Bioequivalence Study of Two Formulations of Sildenafil Tablet 100 mg in Healthy Male Volunteers Under Fasting Conditions

Pharmtechnology

Status and phase: Unknown; Phase 1

Conditions: Bioequivalence

Treatments: Drug: Viagra® film-coated tablet 100 mg; Drug: Sildenafil film-coated tablet 100 mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04882826

SLDF-2020-CPI-FRMT

Details and patient eligibility

About

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 (Viagra®, 100 mg film-coated tablets) or the test (Sildenafil, 100 mg film-coated tablets) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent

Enrollment: 44 estimated patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy caucasian men aged between 18 to 45 years
2. The written consent of the volunteer to be included in the study
3. Verified diagnosis "healthy" according to the anamnesis data and the results of standard clinical, laboratory and instrumental examination methods, physical examination and anamnestic examination
4. Body mass index 18.5-30 kg/m² according to Quetelet's weight-height index
5. 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)
6. Absence of ophthalmological disease according to the data of the ophthalmological examination
7. Consent to use a double barrier method of contraception (condom + spermicide) or sexual continence, as well as consent not to take part in sperm donation from the moment of taking the drug in the first period, during the entire study and within 14 days after taking the drug in the second period research
8. Subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations

Exclusion criteria

1. Burdened allergic history, hypersensitivity to sildenafil or excipients that are part of any of the investigational drugs, or intolerance to these components.
2. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
3. Anatomical deformation of penis (angulation, cavernous fibrosis, or Peyronie's disease).
4. History of priapism.
5. Hereditary retinitis pigmentosa.
6. Episodes of development of anterior non-arteritis ischemic neuropathy of the optic nerve.
7. Organic brain damage, a history of increased convulsive readiness.
8. Acute or chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, and also diseases of the gastrointestinal tract, liver, kidneys and blood, eye disease.
9. 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.
10. The presence of mental disorders, including a history.
11. Surgical interventions on the gastrointestinal tract, with the exception of appendectomy.
12. Acute infectious diseases that ended less than 4 weeks before taking the drug in the first period.
13. Dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study, if vomiting or diarrhea wasn't a manifestation of an infectious disease.
14. 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.
15. Heart rate less than 60 beats/min or more than 90 beats/min at the time of screening, respiratory rate less than 14 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.
16. Use of any prescription and OTC drugs including herbs and food additives, vitamins that can have a significant effect on the PK of sildenafil or data on the effect of which on the pharmacokinetics of sildenafil 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;
17. Use of well-known inhibitors or inducers of liver microsomal enzymes (barbiturates, omeprazole, cimetidine, etc.) or antiviral drugs less than 2 months before enrollment in the study.
18. The use of donors of nitric oxide, organic nitrates or nitrites in any form less than 30 days before taking of the drug in the first period.
19. Donation of plasma or blood (450 ml or more) less than 2 months (60 days) before taking the drug in the first period.
20. 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.
21. Consumption of alcohol and alcohol-containing foods and beverages less than 48 hours before taking the drug in the first period.
22. Use of citrus fruits (including grapefruit and grapefruit juice) and cranberries (including juices, fruit drinks, etc.) less than 7 days before taking the drug in the first period.
23. 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) or history of alcoholism, drug addiction, drug abuse.
24. Intense physical activity less than 24 hours before taking the drug in the first period.
25. Smoking more than 10 cigarettes less than 24 hours before taking the drug in the first period.
26. Participation in other clinical trials of drugs less than 3 months before taking the drug in the first period.
27. Following any low sodium diet within 2 weeks prior to study initiation, or following a special diet (vegetarian, vegan, with limited salt intake) or lifestyle (night work, extreme physical activity).
28. Test positive for syphilis, hepatitis B, hepatitis C or HIV at the time of screening.
29. Positive test for alcohol in exhaled air at screening.
30. Positive urinalysis for the content of narcotic and potent substances during screening (opiates, morphine, barbiturates, benzodiazepines, cannabinoids/marijuana).
31. The value of standard laboratory and instrumental parameters that go beyond the reference values.
32. Lack of intention of volunteers to comply with the Protocol requirements throughout the course of the study and/or lack, in the opinion of the Investigator, of the volunteers' ability to understand and evaluate the information on this study as part of the informed consent form signing process, in particular regarding the expected risks and possible discomfort.
33. Mental, physical and other reasons that do not allow the volunteer to adequately assess their behavior and correctly comply with the conditions of the research protocol.
34. Tattooing and piercing within 30 days prior to first drug administration.
35. Difficulty swallowing tablets.
36. Difficulty with taking blood (for example, difficult access to the veins).

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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44 participants in 2 patient groups

Sequence TR

Other group

Description:

22 subjects assigned to the sequence TR will receive a single 100 mg dose of the test product Sildenafil (1 x 100 mg tablet), marked as T in the sequence, in Period 1 and a single 100 mg dose of the reference product Viagra® (1 x 100 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.

Treatment:

Drug: Sildenafil film-coated tablet 100 mg

Drug: Viagra® film-coated tablet 100 mg

Sequence RT

Other group

Description:

22 subjects assigned to the sequence RT will receive a single 100 mg dose of the reference product Viagra® (1 x 100 mg tablet), marked as R in the sequence, in Period 1 and a single 100 mg dose of the test product Sildenafil (1 x 100 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.

Treatment:

Drug: Sildenafil film-coated tablet 100 mg

Drug: Viagra® film-coated tablet 100 mg