Bioequivalence Study of Two Formulations of Tablets Ramipril 10 mg in Healthy Volunteers Under Fasting Conditions

NCT05438316 | Completed Phase 1

• 1 other identifier: RMP-FT-2022
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-labeled, randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Tritace®, 10 mg tablets) or the test (Ramipril, 10 mg tablets) 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 ramipril and active metabolite ramiprilat 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 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration.

• AUC0-72 of ramipril and ramiprilat 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 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration

Secondary Outcomes (8)

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

  Time points 0.00 (prior to each drug administration) and 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration

• TLQC of ramipril and ramiprilat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration

• AUC 0-INF of ramipril and ramiprilat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration

• Residual area of ramipril and ramiprilat in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration

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

  Time points 0.00 (prior to each drug administration) and 0.10, 0.20, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.30, 3.00, 3.30, 4.00, 4.30, 5.00, 6.00, 8.00, 10.00, 12.00, 15.00, 24.00, 48.00, 72.00 hours after each drug administration

Study Arms (2)

Sequence TR

OTHER

25 subjects assigned to the sequence TR will receive a single 10 mg dose of the test product Ramipril (1 x 10 mg tablet), marked as T in the sequence, in Period 1 and a single 10 mg dose of the reference product Tritace® (1 x 10 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: Ramipril tablet 10 mg; Drug: Tritace® tablet 10 mg

Sequence RT

OTHER

25 subjects assigned to the sequence RT will receive a single 100 mg dose of the reference product Tritace® (1 x 10 mg tablet), marked as R in the sequence, in Period 1 and a single 10 mg dose of the test product Ramipril (1 x 10 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: Ramipril tablet 10 mg; Drug: Tritace® tablet 10 mg

Interventions

Ramipril tablet 10 mg DRUG

Ramipril is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 10 mg of ramipril.

Also known as: The test product

Sequence RT; Sequence TR

Tritace® tablet 10 mg DRUG

Tritace® is manufactured by Sanofi-Aventis Deutschland GmbH, Germany. Each tablet contains 10 mg of ramipril.

Also known as: The reference product

Sequence RT; Sequence TR

Eligibility Criteria

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

You may qualify if:

• Healthy european men or women aged between 18 to 45 years
• Body mass index 18.5-30 kg/m² according to Quetelet's weight-height index
• 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 level of systolic blood pressure (SBP) measured in the sitting position at the time of screening ≥100 mm Hg and ≤ 139 mm Hg and diastolic blood pressure (DBP) ≥ 60 mm Hg or ≤ 90 mm Hg; heart rate more than 60 beats/min and less than 90 beats/min at the time of screening, respiratory rate more than 12 and less than 20 per minute at the time of screening, body temperature above 35.9 ° C and below 36.9 °C at the time of screening
• Subjects are able to understand the requirements of the study
• Subjects are able to accept all the restrictions imposed during the course of the study
• The written consent of the volunteer to be included in the study
• For female subject:
• 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;
• For male: consent to use a double barrier method of contraception (condom + spermicide) or complete sexual abstinence, as well as consent not to participate in sperm donation during the entire study and 30 days after taking the drug in the second period.

You may not qualify if:

• hypersensitivity to any ACE inhibitors, including ramipril or excipients that are part of any of the investigational drugs, or intolerance to these components;
• burdened allergic history
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
• acute infectious diseases or allergic diseases that ended less than 4 weeks before taking the drug in the first period;
• surgical interventions on the gastrointestinal tract, with the exception of appendectomy
• 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 value of standard laboratory and instrumental parameters that go beyond the reference values
• positive test for syphilis, hepatitis B, hepatitis C or HIV at the time of screening;
• positive test for alcohol in exhaled air at screening
• positive urine analysis for the content of narcotic and potent substances during screening (opiates, morphine, barbiturates, benzodiazepines, cannabinoids/marijuana)
• for women - positive pregnancy test at screening
• adherence to any low-sodium diet within 2 weeks prior to taking the drug in the first study period, or adherence to a special diet (vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical exercise)
• intake of more than 10 units alcohol per week (1 unit of alcohol is equivalent to 500 ml of beer, 200 ml of dry wine or 50 ml of spirits ethyl 40%) or history of alcoholism, drug addiction, drug abuse;
• inability to go without food for at least 12 hours and the inability to take the drug on an empty stomach;

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• Ligand Research, LLC: collaborator

Study Sites (1)

Ligand Research LLC

Moscow, 115419, Russia

Location

MeSH Terms

Interventions

Ramipril

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sergey Filatov

  Ligand Research, LLC

  STUDY DIRECTOR

• Irina Rodiukova

  Ligand Research, 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: June 24, 2022
• First Posted: June 29, 2022
• Study Start: June 17, 2022
• Primary Completion: August 2, 2022
• Study Completion: November 17, 2022
• Last Updated: June 29, 2023

Record last verified: 2023-06

Locations

RU (1)