Bioequivalence of Trienor

• Register: RPCEC
• Last refreshed on: 29 April 2024
• Main ID: RPCEC00000265
• Date of registration: 30/01/2018
• Prospective Registration: Yes
• Primary sponsor: Center for Pharmaceutical Research and Development, Havana, Cuba.
• Public title: Bioequivalence of Trienor
• Scientific title: Bioequivalence study of a formulation of Trienor in healthy volunteers
• Date of first enrolment: 01/08/2018
• Target sample size: 72
• Recruitment status: Pending
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000265-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Double Blind. Control group: Active. Assignment: Crossover. Purpose: Other
• Phase: 1

Countries of recruitment

Cuba

Contacts

• Name: Idrian Garcia Garcia
• Affiliation: Center for Pharmaceutical Research and Development

• Name: Idrian Garcia Garcia
• Affiliation: Center for Pharmaceutical Research and Development

Key inclusion & exclusion criteria

Inclusion criteria: 1- Written informed consent.
2- Aged between 18-50 years.
3- Male subjects.
4- Volunteers’ weight: +/- 15% of their ideal weight for height.
5- Failure to submit evidence of organic or psychiatric disease according to interrogation, physical examination and laboratory tests.
6- Not have evidence or history of diseases such as bronchial asthma, hypertension, bad-absorption syndrome, peptic ulcer or duodenal present, liver failure, kidney failure, severe allergic reactions, atopic dermatitis, cardiovascular disorders, diabetes mellitus.
7- Satisfactory physical examination.
8- Present vital signs values within the following reference ranges. Systolic blood pressure between 90 and 130 mm Hg and diastolic blood pressure between 60 and 80 mm Hg, heart rate between 60 to 100 beats per minute, respiratory rate between 12 to 20 breaths per minute.
9- Not having consumed alcohol, drinks containing xanthines (tea, coffee, and cola) and carbonated beverages three days before the start of each period and during it.
10- Smoking or non-smoking subjects. A record of cigars use will be made.
11- Laboratory results within the acceptance range. For some parameters such as blood counts with differential, urine, etc., a result found outside the reference range will be carefully evaluated by the clinical investigator.
Exclusion criteria: 1- Failure to comply with any of the inclusion criteria.
2- History of allergy, idiosyncratic or hypersensitivity to levonorgestrel or etinilestradiol or the components of the formulations under study.
3- Refer some viral disease in the last 7 days.
4- To be ingesting some medication 15 days (or for 5 half-lives) before the first dose of product research or nonprescribed or free drugs (OTC drugs) or herbal medicines / dietary supplements in a period seven days before the first dose of research products until the end of the study.
5- Total bilirubin values hihger than 1.5 times the upper limit of the reference range.
6- Serum creatinin values higher than 1.5 times the upper limit of the reference range.
7- Values of AST, ALT and GGT higher than 2 times the upper limit of the reference range.
8- Positive for hepatitis B and C virus, HIV or serology.
9- History of alcoholism in the past 6 months (not less consumption ¼ bottle of rum or one (1) bottle of wine or three (3) beers in a higher frequency of twice a week.
10- Patients with a history of drug consumption dependence or drug abuse.
11- Blood donation 3 months prior to baseline.
12- Participation in a clinical trial in the last 6 months.
13- To be undergone major surgery within 6 months prior to baseline.
14- History or antecedents of drug allergy.

Age minimum: 18 years
Age maximum: 50 years
Gender: Male

Health Condition(s) or Problem(s) studied

Healthy volunteers

Intervention(s)

Administration, Oral

Ethinyl Estradiol

Estrogens

Single Dose

Group Trienor and then Triquilar: Subjects will receive
a unique dose of 0.03 mg of etinilestradiol and 0.05 mg of levonorgestrel, or
a unique dose of 0.04 mg of etinilestradiol and 0.075 mg of levonorgestrel, or
a unique dose of 0.03 mg of etinilestradiol and 0.125 mg of levonorgestrel (one tablet of Trienor) by oral route between 8:00 and 9:00 am.
After a washout period of 7 days, they will receive
a unique dose of 0.03 mg of etinilestradiol and 0.05 mg of levonorgestrel, or
a unique dose of 0.04 mg of etinilestradiol and 0.075 mg of levonorgestrel, or
a unique dose of 0.03 mg of etinilestradiol and 0.125 mg of levonorgestrel (one tablet of Triquilar) by oral route between 8:00 and 9:00 am too.

Group Triquilar and then Trienor: Subjects will receive
a unique dose of 0.03 mg of etinilestradiol and 0.05 mg of levonorgestrel, or
a unique dose of 0.04 mg of etinilestradiol and 0.075 mg of levonorgestrel, or
a unique dose of 0.03 mg of etinilestradiol and 0.125 mg of levonorgestrel (one tablet of Triquilar) by oral route between 8:00 and 9:00 am.
After a washout period of 7 days, they will receive
a unique dose of 0.03 mg of etinilestradiol and 0.05 mg of levonorgestrel, or
a unique dose of 0.04 mg of etinilestradiol and 0.075 mg of levonorgestrel, or
a unique dose of 0.03 mg of etinilestradiol and 0.125 mg of levonorgestrel (one tablet of Trienor) by oral route between 8:00 and 9:00 am too.

Therefore, the study will comprise six periods of treatments.

Levonorgestrel

Progestins

Trienor, Triquilar

Tablets

Primary Outcome(s)

Pharmacokinetic variable
- Plasma levels of Levonorgestrel and Etinilestradiol (values expressed in ng/mL): Measuring time: At baseline and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72 and 96 hours after administration.

Secondary Outcome(s)

- Presence of adverse events (AE) (distribution frequency for the appearance of adverse events (Yes, No), type of event (name of the AE), duration (time from appearance to end of the event), severity (severe, non-severe), intensity of AE (grades 1-5), relation of causality (remote, possible, probable, very probable), result of AE (recuperate, improvement, persist or sequels), attitude concerning the studied treatment (without changes, dose modification, temporal or definitive treatment discontinuation). Measuring time: At each administration and during the whole study.
- Clinical laboratory tests: Hematology (hemoglobin, hematocrit, erythrocytes count, white blood cells counts, platelet count) and Biochemistry (glycemia, cholesterol, triglycerides, transaminases, alkaline phosphatase, urea, creatinine, total proteins, total bilirubin) determinations (numerical values as units of measurement for each determination). Measuring time: At baseline and end of the study.
- Vital signs (body temperature in degrees centigrade, heart rate in beats / minute, blood pressure in mm Hg and respiration rate in breaths per minute). Measuring time: Prior to administration of the tablets, during the first 4 hours after administration, and at the end of each period.

Secondary ID(s)

BB/02/16

Source(s) of Monetary Support

BioCubaFarma

Secondary Sponsor(s)

UEB Reinaldo Gutierrez, Company MEDSOL, BioCubaFarma, Havana, Cuba.