Bioequivalence of Trienor

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Bioequivalence study of a formulation of Trienor in healthy volunteers

Secondary indentifying numbers:

BB/02/16

Issuing authority of the secondary identifying numbers:

Center for Pharmaceutical Research and Development, Havana, Cuba.

Source(s) of monetary or material support:

BioCubaFarma

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Reference number:

In process

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Carlos

Midle name:

Alberto

Last name:

Gonzalez Delgado

Medical Specialty :

Second degree specialist in Pharmacology. Master in Experimental Pharmacology.

Affiliation:

National Center of Toxicology (CENATOX)

Postal address:

Ave. 31 and 114 st., Marianao.

City:

Havana

Country:

Cuba

Zip Code:

11400

Telephone:

+53-72743282

Email address:

eclinicos@infomed.sld.cu [1]

carglez@infomed.sld.cu [2]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Not applicable

Research ethics committees:

National Center of Toxicology, March 25, 2016.

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

01/08/2018

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Healthy volunteers

Health condition(s) code:

Healthy Volunteers

Intervention(s):

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.

Intervention code:

Ethinyl Estradiol

Levonorgestrel

Estrogens

Progestins

Tablets

Administration, Oral

Single Dose

Intervention keyword:

Trienor, Triquilar

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

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.

Key secondary outcomes:

- 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.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male

Minimum age:

18 years

Maximum age:

50 years

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.

Type of population:

Adults

Type of participant:

Healthy volunteers

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Other

Other purpose:

To demonstrate bioequivalence of domestic generic formulation Trienor with the leading drug in healthy volunteers

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Active

Study design:

Crossover

Phase:

Target sample size:

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Idrian

Last Name:

Garcia Garcia

Specialty:

PhD in Health Sciences. Bachelor in Pharmaceutical Sciences. Master in Experimental Pharmacology. Assistant researcher.

Affiliation:

Center for Pharmaceutical Research and Development

Postal Address:

Ave. 26 and Calzada de Grandes Puentes, # 1605, Plaza de la Revolución.

City:

Havana

Country:

Cuba

Zip Code:

10600

Telephone:

+53-78811944 ext. 144.

Email :

idrian.garcia@cidem.cu [3]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Idrian

Last Name:

Garcia Garcia

Specialty:

PhD in Health Sciences. Bachelor in Pharmaceutical Sciences. Master in Experimental Pharmacology. Assistant researcher.

Affiliation:

Center for Pharmaceutical Research and Development

Postal Address:

Ave. 26 and Calzada de Grandes Puentes, #1605, Plaza de la Revolución.

City:

Havana

Country:

Cuba

Zip Code:

10600

Telephone:

+53-78811944 ext. 144.

Email :

idrian.garcia@cidem.cu [3]

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000265

Date of Registration in Primary Registry:

30/01/2018

Record Verification Date:

2018/01/30

Next update date:

2019/01/30

Link to the spanish version:

Click here [4]