Comparative Pharmacodynamics and Pharmacodynamics Equivalence of Antareit 800 mg Chewable Tablets and Riopan 800 mg Chewable Tablets in Healthy Volunteers

An Open-label, Randomized, Crossover Study to Investigate the Comparative Pharmacodynamics and Pharmacodynamics Equivalence of Antareit 800 Chewable Tablets and Riopan 800 mg Chewable Tablets in Healthy Volunteers

Comparative study of the pharmacodynamic parameters and pharmacodynamic equivalence (bioequivalence) of drug Antareit 800 mg chewable tablets and drug Riopan 800 mg chewable tablets in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Heartburn; Acid-dependent Diseases of the Gastrointestinal Tract; Symptomatic Treatment of Gastric and Duodenal Ulcers
• Intervention / Treatment: Drug: Magaldrate; Drug: Magaldrate

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 109235
    • Llc "Certa Clinic"
  • Saint Petersburg, Russian Federation, 196143
    • Limited Liability Company "Research Center Eco-Safety"
  • Saint Petersburg, Russian Federation, 195271
    • Private Health Care Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary and handwritten informed consent form signed by a healthy volunteer to participate in the study prior to any of the study procedures;
2. Healthy male and female caucasian volunteers aged 18 to 45 years (inclusive);
3. Verified diagnosis "healthy" (without abnormal findings in the protocol-defined clinical, laboratory, and instrumental test data);
4. pH according to hourly pH-metry in the screening period, carried out at least 3 hours after the last meal, is completely in the range from 1 to 3 inclusive throughout the entire astronomical hour of measurement;
5. Blood pressure (BP) levels: 100 to 139 mm Hg, inclusive (systolic, SBP), 60 to 89 mm Hg, inclusive (diastolic, DBP);
6. Heart rate (HR) of 60 to 90 bpm, inclusive;
7. Body mass index (BMI) of 18.5 kg/m2 ≤ BMI ≤ 30 kg/m2, where the body weight range is ≥ 55 kg for men and ≥ 45 kg for women;
8. Non-smoking healthy volunteers (who have never smoked or gave up smoking more than 6 months prior to the Screening);
9. Consent to use adequate methods of contraception throughout the study and for 30 days after completion; for women of preserved reproductive potential, a negative urine pregnancy test result;
10. The volunteers must have adequate behavior and coherent speech.

Exclusion Criteria:

1. A history of allergy;
2. History of drug intolerance to the active substance and/or excipients included in the study drugs;
3. History of drug intolerance of or hypersensitivity/allergic reactions to lidocaine, xylocaine or other topical anesthetics which will be used at the trial site for anesthesia during esophagogastroduodenoscopy (EGD) and insertion of the probe for the pH measurements;
4. Chronic diseases of the circulatory, lymphatic, respiratory, nervous, endocrine, gastrointestinal, musculoskeletal, integumentary, immune, urogenital, and hematopoietic systems;
5. Esophageal, gastric, and/or duodenal diseases based on EGD performed at screening and based on the medical history; a history of esophageal, gastric, and/or duodenal surgery;
6. Diseases/conditions which, in the opinion of the investigator, may affect the pH measurement results;
7. Acute infectious diseases less than 4 weeks prior to screening;
8. Use of antacids (including sodium bicarbonate solution)/H2 antagonists 24 h prior to the Screening Visit;
9. Use of proton pump inhibitors 72 h prior to the Screening Visit;
10. Use of (including use of a single dose) steroids and/or other ulcerogenic drug (e.g., nonsteriodal anti-inflammatory drugs [NSAID]) less than 4 weeks prior to the Screening Visit;
11. Regular use of any medicinal products, including prescription only and OTC (Over-the-counter) drugs and dietary supplements within 2 weeks prior to the Screening Visit;
12. Blood or plasma donation less than 3 months prior to the Screening Visit;
13. Use of hormonal contraceptives (in women) less than 2 months prior to the Screening Visit;
14. Pregnancy or breastfeeding; a positive pregnancy test for women of childbearing potential;
15. Participation in another clinical trial less than 3 months prior to screening or simultaneously with this study;
16. Use of more than 10 units of alcohol (1 unit of alcohol is equivalent to 330 ml of beer, 150 ml of wine or 40 ml of spirits) a week within a month prior to the enrollment in the study or history data of alcohol/drug dependence or drug abuse.
17. Positive antibody blood test for HIV-1 and HIV-2, Treponema pallidum antigen, hepatitis B surface antigen (HBsAg), or hepatitis C virus antigen;
18. Positive urine test for narcotic substances or strong drugs;
19. Positive test for alcohol vapor in exhaled breath or a positive alcohol saliva test;
20. Deviated septum/nasal obstruction preventing the placement of the pH probe;
21. Medical history of chronic constipation;
22. Medical history of severe maxillofacial injuries;
23. Expected admission to hospital during this study for any reason, except for hospitalization provided for by this protocol;
24. Impossibility or failure to comply with the protocol, undergo protocol-defined procedures, or adhere to the diet or activity regime;
25. Other circumstances which in the opinion of the investigator prevent a volunteer from being included in the study or may result in premature drop-out from the study.

Withdrawal criteria:

1. The volunteer's refusal to further participate in the study;
2. Failure of the volunteer to comply with the rules of participation in the study (skipping study procedures, independent use of drugs prohibited in the study, violation of dietary and lifestyle restrictions, etc.);
3. Taking prohibited therapy;
4. Occurrence of causes/occurrence during the study of situations that threaten the safety of the volunteer, including severe AEs;
5. Volunteers selected to participate in the study in violation of the inclusion/non-inclusion criteria;
6. Violation of the rules for conducting pH measurements or the occurrence of conditions that required early termination of pH measurements (vomiting, nosebleeds, etc.);
7. Missing a dose of the study drug/comparator drug during any period of the study for any reason;
8. Positive urine test for narcotics and strong drugs;
9. Positive breath alcohol vapor test or alcohol in saliva;
10. Positive pregnancy test in women;
11. The occurrence in the course of the study of other reasons that prevent the study according to the protocol.

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: TR-sequence (T-test drug, R-reference drug); Group 1 (20 volunteers, TR sequence) will take 2 tablets of Antareit (magaldrate) 800 mg chewable tablets 2 h prior to food intake in Period 1 and 2 tablets of Riopan (magaldrate) 800 mg chewable tablets 2 h prior to food intake in Period 2	Drug: Magaldrate; A dose of T drug in one of 2 periods of the study 2 h prior to food intake, 3 times per day; Other Names: Antareit (T); Drug: Magaldrate; A dose of R drug in one of 2 periods of the study 2 h prior to food intake, 3 times per day; Other Names: Riopan (R)
Experimental: RT-sequence; Group 2 (20 volunteers, RT sequence) will take 2 tablets of Riopan (magaldrate) 800 mg chewable tablets 2 h prior to food intake in Period 1 and 2 tablets of Antareit (magaldrate) 800 mg chewable tablets 2 h prior to food intake in Period 2	Drug: Magaldrate; A dose of T drug in one of 2 periods of the study 2 h prior to food intake, 3 times per day; Other Names: Antareit (T); Drug: Magaldrate; A dose of R drug in one of 2 periods of the study 2 h prior to food intake, 3 times per day; Other Names: Riopan (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics - AUCpH - Area under the curve potential of hydrogen above the baseline	Area under the pharmacodynamic pH-time curve adjusted to baseline (before drug intake)	From 0 to 1 hour (Day 1 and Day 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability: adverse event (AE) number and frequency	Number and frequency of adverse events (AEs) or serious AEs (SAEs)	From the screening (and signing informed consent form) to Day 15 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: serious adverse event (SAE) number and frequency	Number and frequency of serious AEs (SAEs)	From the screening (and signing informed consent form) to Day 15 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 15)
Pharmacodynamics - time percentage during which the intragastric pH value will exceed 4.0	PH - potential of hydrogen	From 0 to 1 hour (Day 1 and Day 8)
Pharmacodynamics - рН maximum	Maximum potential of hydrogen	From 0 to 1 hour (Day 1 and Day 8)
Pharmacodynamics - рН minimum	Minimum potential of hydrogen	From 0 to 1 hour (Day 1 and Day 8)
Pharmacodynamics - average pH value	Root mean square	From 0 to 1 hour (Day 1 and Day 8)
Pharmacodynamics - time percentage during which the intragastric pH value will exceed 3.0	Time during which the intragastric pH value will exceed 3.0	From 0 to 1 hour (Day 1 and Day 8)
Pharmacodynamics - median time when the pH was above 3.0	Time during which the intragastric pH value will be above 3.0	From 0 to 1 hour (Day 1 and Day 8)
Pharmacodynamics - median time when the pH was above 4.0	Time during which the intragastric pH value will be above 4.0	From 0 to 1 hour (Day 1 and Day 8)
Safety and Tolerability: volunteer complaints	Description of complaints, recieved from volunteer	From the screening (and signing informed consent form) to Day 15 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - cardiovascular system	An assessment of the condition of the cardiovascular system on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - respiratory system	An assessment of the condition of the respiratory system on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - digestive tract	An assessment of the condition of the digestive tract on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - endocrine system	An assessment of the condition of the endocrine system on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - musculoskeletal system	An assessment of the condition of the musculoskeletal system on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - nervous system	An assessment of the condition of the nervous system on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - sensory systems	An assessment of the condition of the sensory systems on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: physical examination results - skin/visible mucous membranes	An assessment of the condition of the skin/visible mucous membranes on physical examination (normal condition or list of abnormal conditions, if any)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: vital signs - systolic blood pressure	Systolic blood pressure (SBP, mmHg)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: vital signs - diastolic blood pressure	Diastolic blood pressure (DBP, mmHg)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: vital signs - heart rate	Heart rate (HR, bpm)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: vital signs - body temperature (Celsius temperature scale)	Body temperature (Celsius temperature scale)	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 15)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: heart rate (beats per minute)	Screening, Day 9
Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: PQ interval (is the period, measured in milliseconds, that extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex)	Screening, Day 9
Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: QRS complex (the QRS complex is the combination of three of the graphical deflections seen on a typical electrocardiogram)	Screening, Day 9
Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: corrected QT interval (distance from the beginning of the QRS complex to the end of the T wave)	Screening, Day 9
Safety and Tolerability: clinical blood test - hemoglobin	Hemoglobin (g/L)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - hematocrit	hematocrit (%)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - red blood cell count	Red blood cell count (cells/L)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - platelet count	Platelet count (cells/L)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - leukocyte count	Leukocyte count (cells/L)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate	Erythrocyte sedimentation rate (m/h)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - myelocytes	Leukocyte formula (myelocytes, %)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - band neutrophils	Leukocyte formula (band neutrophils, %)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - segmented neutrophils	Leukocyte formula (segmented neutrophils, %)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - eosinophils	Leukocyte formula (eosinophils, %)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - basophils	Leukocyte formula (basophils, %)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - monocytes	Leukocyte formula (monocytes, %)	Screening, Day 2, Day 9
Safety and Tolerability: clinical blood test - lymphocytes	Leukocyte formula (lymphocytes, %)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - glucose	Glucose concentration (mmol/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - cholesterol	Total cholesterol concentration (mmol/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - protein	Total protein concentration (g/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - bilirubin	Total bilirubin concentration (micromol/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - creatinine	Creatinine concentration (micromol/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - alkaline phosphatase	Alkaline phosphatase activity (U/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - alanine transaminase	Alanine transaminase activity (U/L)	Screening, Day 2, Day 9
Safety and Tolerability: blood chemistry - aspartate transaminase	Aspartate transaminase activity (U/L)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - specific gravity	Specific gravity of the urine	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - color	Color of the urine	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - transparency	Transparency of the urine	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - pH	pH of the urine	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - protein	Protein concentration (g/L)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - glucose	Glucose concentration (mmol/L)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - red blood cells	Red blood cell content (number in sight)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - white blood cells	White blood cell content (number in sight)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - epithelial cells	Epithelial cell content (number in sight)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - casts	Presence of casts (Yes/No)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - mucus	Presence of mucus (Yes/No)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis - bacteria	Presence of bacteria (Yes/No)	Screening, Day 2, Day 9
Safety and Tolerability: urinalysis (microscopy)	Microscopy of urine sediment is performed if it is present	Screening, Day 2, Day 9

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: July 19, 2024
• First Submitted That Met QC Criteria: August 9, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Duodenal Ulcer; Heartburn; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Magnesium Hydroxide; Aluminum Hydroxide; Magaldrate
• Other Study ID Numbers: ANT-05-02-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No