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

Not Applicable

Completed

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

• Registration Number: NCT06552624
• Lead Sponsor: Valenta Pharm JSC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-07
• Primary Completion: 2022-08-31
• Study Completion: 2022-08-31
• Study First Submitted: 2024-07-19
• Status Verified: 2024-08
• Study First Submitted QC: 2024-08-09
• Last Update Submitted: 2024-08-09
• Study First Posted: 2024-08-14
• Last Update Posted: 2024-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
TR-sequence (T-test drug, R-reference drug)	Magaldrate	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
RT-sequence	Magaldrate	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics - рН minimum	From 0 to 1 hour (Day 1 and Day 8)	Minimum potential of hydrogen
Pharmacodynamics - average pH value	From 0 to 1 hour (Day 1 and Day 8)	Root mean square
Safety and Tolerability: physical examination results - endocrine system	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)	An assessment of the condition of the endocrine system on physical examination (normal condition or list of abnormal conditions, if any)
Safety and Tolerability: physical examination results - nervous system	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)	An assessment of the condition of the nervous system on physical examination (normal condition or list of abnormal conditions, if any)
Safety and Tolerability: physical examination results - sensory systems	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)	An assessment of the condition of the sensory systems on physical examination (normal condition or list of abnormal conditions, if any)
Pharmacodynamics - time percentage during which the intragastric pH value will exceed 4.0	From 0 to 1 hour (Day 1 and Day 8)	PH - potential of hydrogen
Safety and Tolerability: physical examination results - cardiovascular system	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)	An assessment of the condition of the cardiovascular system on physical examination (normal condition or list of abnormal conditions, if any)
Safety and Tolerability: physical examination results - respiratory system	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)	An assessment of the condition of the respiratory system on physical examination (normal condition or list of abnormal conditions, if any)
Pharmacodynamics - рН maximum	From 0 to 1 hour (Day 1 and Day 8)	Maximum potential of hydrogen
Pharmacodynamics - time percentage during which the intragastric pH value will exceed 3.0	From 0 to 1 hour (Day 1 and Day 8)	Time during which the intragastric pH value will exceed 3.0
Pharmacodynamics - median time when the pH was above 4.0	From 0 to 1 hour (Day 1 and Day 8)	Time during which the intragastric pH value will be above 4.0
Safety and Tolerability: physical examination results - digestive tract	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)	An assessment of the condition of the digestive tract on physical examination (normal condition or list of abnormal conditions, if any)
Safety and Tolerability: physical examination results - musculoskeletal system	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)	An assessment of the condition of the musculoskeletal system on physical examination (normal condition or list of abnormal conditions, if any)
Safety and Tolerability: vital signs - 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)	Body temperature (Celsius temperature scale)
Pharmacodynamics - median time when the pH was above 3.0	From 0 to 1 hour (Day 1 and Day 8)	Time during which the intragastric pH value will be above 3.0
Safety and Tolerability: adverse event (AE) number and frequency	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)	Number and frequency of adverse events (AEs) or serious AEs (SAEs)
Safety and Tolerability: physical examination results - skin/visible mucous membranes	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)	An assessment of the condition of the skin/visible mucous membranes on physical examination (normal condition or list of abnormal conditions, if any)
Safety and Tolerability: vital signs - diastolic blood pressure	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)	Diastolic blood pressure (DBP, mmHg)
Safety and Tolerability: serious adverse event (SAE) number and frequency	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)	Number and frequency of serious AEs (SAEs)
Safety and Tolerability: volunteer complaints	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)	Description of complaints, recieved from volunteer
Safety and Tolerability: clinical blood test - myelocytes	Screening, Day 2, Day 9	Leukocyte formula (myelocytes, %)
Safety and Tolerability: vital signs - systolic blood pressure	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)	Systolic blood pressure (SBP, mmHg)
Safety and Tolerability: vital signs - heart rate	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)	Heart rate (HR, bpm)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex	Screening, Day 9	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)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval	Screening, Day 9	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)
Safety and Tolerability: clinical blood test - hemoglobin	Screening, Day 2, Day 9	Hemoglobin (g/L)
Safety and Tolerability: clinical blood test - hematocrit	Screening, Day 2, Day 9	hematocrit (%)
Safety and Tolerability: clinical blood test - red blood cell count	Screening, Day 2, Day 9	Red blood cell count (cells/L)
Safety and Tolerability: clinical blood test - platelet count	Screening, Day 2, Day 9	Platelet count (cells/L)
Safety and Tolerability: clinical blood test - leukocyte count	Screening, Day 2, Day 9	Leukocyte count (cells/L)
Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate	Screening, Day 2, Day 9	Erythrocyte sedimentation rate (m/h)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval	Screening, Day 9	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)
Safety and Tolerability: clinical blood test - eosinophils	Screening, Day 2, Day 9	Leukocyte formula (eosinophils, %)
Safety and Tolerability: clinical blood test - basophils	Screening, Day 2, Day 9	Leukocyte formula (basophils, %)
Safety and Tolerability: clinical blood test - monocytes	Screening, Day 2, Day 9	Leukocyte formula (monocytes, %)
Safety and Tolerability: clinical blood test - lymphocytes	Screening, Day 2, Day 9	Leukocyte formula (lymphocytes, %)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate	Screening, Day 9	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)
Safety and Tolerability: clinical blood test - band neutrophils	Screening, Day 2, Day 9	Leukocyte formula (band neutrophils, %)
Safety and Tolerability: clinical blood test - segmented neutrophils	Screening, Day 2, Day 9	Leukocyte formula (segmented neutrophils, %)
Safety and Tolerability: blood chemistry - glucose	Screening, Day 2, Day 9	Glucose concentration (mmol/L)
Safety and Tolerability: blood chemistry - cholesterol	Screening, Day 2, Day 9	Total cholesterol concentration (mmol/L)
Safety and Tolerability: blood chemistry - protein	Screening, Day 2, Day 9	Total protein concentration (g/L)
Safety and Tolerability: blood chemistry - bilirubin	Screening, Day 2, Day 9	Total bilirubin concentration (micromol/L)
Safety and Tolerability: blood chemistry - creatinine	Screening, Day 2, Day 9	Creatinine concentration (micromol/L)
Safety and Tolerability: blood chemistry - alkaline phosphatase	Screening, Day 2, Day 9	Alkaline phosphatase activity (U/L)
Safety and Tolerability: blood chemistry - alanine transaminase	Screening, Day 2, Day 9	Alanine transaminase activity (U/L)
Safety and Tolerability: blood chemistry - aspartate transaminase	Screening, Day 2, Day 9	Aspartate transaminase activity (U/L)
Safety and Tolerability: urinalysis - specific gravity	Screening, Day 2, Day 9	Specific gravity of the urine
Safety and Tolerability: urinalysis - color	Screening, Day 2, Day 9	Color of the urine
Safety and Tolerability: urinalysis - transparency	Screening, Day 2, Day 9	Transparency of the urine
Safety and Tolerability: urinalysis - pH	Screening, Day 2, Day 9	pH of the urine
Safety and Tolerability: urinalysis - protein	Screening, Day 2, Day 9	Protein concentration (g/L)
Safety and Tolerability: urinalysis - glucose	Screening, Day 2, Day 9	Glucose concentration (mmol/L)
Safety and Tolerability: urinalysis - red blood cells	Screening, Day 2, Day 9	Red blood cell content (number in sight)
Safety and Tolerability: urinalysis - white blood cells	Screening, Day 2, Day 9	White blood cell content (number in sight)
Safety and Tolerability: urinalysis - epithelial cells	Screening, Day 2, Day 9	Epithelial cell content (number in sight)
Safety and Tolerability: urinalysis - casts	Screening, Day 2, Day 9	Presence of casts (Yes/No)
Safety and Tolerability: urinalysis - mucus	Screening, Day 2, Day 9	Presence of mucus (Yes/No)
Safety and Tolerability: urinalysis - bacteria	Screening, Day 2, Day 9	Presence of bacteria (Yes/No)
Safety and Tolerability: urinalysis (microscopy)	Screening, Day 2, Day 9	Microscopy of urine sediment is performed if it is present

Trial Locations

Locations (3)

Limited Liability Company "Research Center Eco-Safety"; 🇷🇺 Saint Petersburg, Russian Federation

Llc "Certa Clinic"; 🇷🇺 Moscow, Russian Federation

Private Health Care Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg; 🇷🇺 Saint Petersburg, Russian Federation