Clinical trial NCT02758912: Clinical Study of Medicinal Product Cardionat® Using in Health Athlete Volunteers
Official title: Open-label Clinical Pharmacokinetic Study of Cardionat®, Capsules 250 mg (JSC Nizhpharm, Russia) Using in Health Athlete Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stroke, Not Specified as Hemorrhage or Infarction
Angina Pectoris
Lead sponsor: Burnasyan Federal Medical Biophysical Center
Sponsor class: OTHER_GOV
First posted: 2016-05-03
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to evaluate the long-term plasma and urine pharmacokinetic parameters of Cardionat®, capsules 250 mg, when used in healthy athlete volunteers.

The study consists of four steps:

* Step 1. Screening - selecting healthy volunteers for inclusion in the study;
* Step 2. Assignment in one of the study group, prescription of the study drug;
* Step 3. Samples collections for pharmacokinetic analysis;
* Step 4. Evaluation of pharmacokinetic data.

Detailed description: Cardionat is a structural analogue of gamma-butyrobetaine - a substance that is in every cell of the human body.

Under extra strain conditions cardionat restores the balance between oxygen delivery to the cell and cellular oxygen demand. Cardionat clears the intracellular accumulation of toxic metabolic products, protecting them from damage; also it has a general tonic effect. As a result of its use of the body acquires the ability to withstand stress and to quickly restore energy reserves. Because of these properties cardionat used to treat a variety of disorders of the cardiovascular system, disorders of blood supply to the brain, as well as to improve physical and mental performance. Synthesis of gamma-butyrobetaine, which has vasodilating properties, is highly increased as a result of reducing the concentration of carnitine.

In the case of acute ischemic myocardial injury cardionat slows the formation of necrotic areas, shortens the rehabilitation period.

In heart failure it increases myocardial contractility, increases exercise tolerance, reduces the frequency of angina attacks. In acute and chronic ischemic cerebrovascular disorders it improves blood circulation in the ischemic areas; it promotes blood redistribution increasing supply of the ischemic areas. It is effective in the case of vascular and dystrophic pathology of the ocular fundus. The drug eliminates functional disturbances of the nervous system in patients with chronic alcoholism during abstinence syndrome.

Pharmacokinetics After oral administration, the drug is rapidly absorbed. Bioavailability is 78%. The maximum plasma concentration is reached 1-2 hours after oral ingestion. The drug is metabolized in the body with the formation of two major metabolites, which are excreted by the kidneys. The half-life after oral intake is dose-dependent, and is usually 3 to 6 hours.

Indications for use:

As a part of combination treatment of coronary heart disease (angina, myocardial infarction), congestive heart failure and dyshormonal cardiomyopathy, as well as part of combination treatment of acute and chronic cerebrovascular disorders (stroke and cerebrovascular insufficiency).

Reduced working capacity; physical stress, including physical stress in athletes.

Abstinence syndrome in chronic alcohol abusers (in combination with specific alcohol abuse therapy).

In this study, volunteers will receive study medication in the form of oral capsules 250 mg.

The study drug will be applied as follows:

* Group 1: intake of study medication capsules orally at a dose of 1 g per day for 3 weeks - 14 volunteers (7 males and 7 females);
* Group 2: intake of study medication capsules at a dose of 2 g per day for 3 weeks - 14 volunteers (7 males and 7 females).

Study results will be published in "Drug Testing and Analysis" journal

Eligibility criteria: Inclusion Criteria:

1. Healthy volunteers of both sexes aged 18 to 35 years old, caucasians;
2. At least 1st sports category among adults;
3. Verified diagnosis "healthy" according to a detailed medical history, and according to standard clinical, laboratory and instrumental methods of examination;
4. BMI should be between 18.5 to 30 kg / m2;
5. Signed Volunteer information sheet with the Informed consent form;
6. Agreement of volunteer to use adequate methods of contraception (contraceptive reliability over 90%: the cervical cap with spermicide, diaphragm with spermicide, condoms, intrauterine devices), or total abstinence from sexual activity for the period of the study:

   * For women during the whole period from 30 days prior to the signing a Volunteer's information sheet with Informed consent form to 30 days after completion of study participation; in the period from the date of signing the Informed consent up to 30 days after completion of study participation barrier method of contraception should be used, if it is not the main method;
   * For men during the whole period from signing a Volunteer's information sheet with the Informed consent form and until the completion of the study barrier method of contraception should be used.

Non - inclusion criteria:

1. Allergy in the past;
2. Drug intolerance, hypersensitivity to any component of the study drug;
3. Chronic cardiovascular, bronchopulmonary, endocrine or nervous systems diseases (including psychiatric disorders), and diseases of the gastrointestinal tract (GIT), liver, kidney, blood disorders, surgical interventions on the gastrointestinal tract (except appendectomy);
4. Fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency;
5. Poor developed superficial veins of the forearm;
6. Acute infectious, non-infectious and allergic diseases in less than 4 weeks prior to Visit 1 (screening);
7. Positive blood test for HIV, syphilis, hepatitis B and C;
8. Intake of more than 10 units of alcohol per week (1 unit of alcohol is equivalent to 1/2 liters of beer, 200 ml wine or 50 ml of spiritus) alcoholism, drug addiction or drug abuse in the past;
9. Smoking more than 10 cigarettes per day;
10. Systolic blood pressure measured in the "sitting" position below 100 mm Hg or above 130 mm Hg and/or diastolic blood pressure below 60 mm Hg or above 90 mm Hg;
11. Heart rate below 40 beats / min;
12. Any deviation from the normal range of the results of clinical and laboratory tests (complete blood count, urinalysis, blood chemistry) and instrumental tests (ECG);
13. Intake of any medicines, including any supplements, not agreed with study doctor;
14. Blood donation: 0-49 ml - 0 days prior to Visit 1 (screening); 50-449 ml - in less than 30 days prior to Visit 1; 450-800 ml or more - less than 60 days prior to Visit 1; 800 ml - by the decision of the Chief Investigator, if the period of time prior to the visit 1 is more than 60 days;
15. Plasmapheresis in less than 14 days prior to Visit 1;
16. Participation in the competitions, where doping tests are required, while participating in this clinical trial (within 6 ± 2 months from the date of inclusion in the study - Visit 1 (Screening));
17. Participation in the study of another medicinal product or medical device in less than 3 months prior to the study;
18. Volunteer's inability or unwillingness to comply with the study protocol requirements;
19. Any reason, which, according to researcher opinion, will impede the participation of volunteer in the study;
20. Pregnant or lactating women (all women should have a negative pregnancy test results on the day of screening).

Exclusion Criteria:

1. Unexpected and previously unknown adverse reactions (if it is related to support volunteer's health);
2. Occurrence of SAEs;
3. Acute diseases or conditions that are not SAEs, but according to researchers opinion, require exclusion of volunteers from the study;
4. Decision to volunteer to withdraw from the study;
5. Violation by volunteer of prescribed regimen and violation of research restrictions (by the decision of the investigator);
6. Investigator's decision to exclude the volunteer from the study

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 3 weeks after assignment of all eligible volunteers to one of the study groups (day 22th)
Secondary outcomes:
measure: Cardionat® levels in blood
timeFrame: following days 0, 22, 26, 33, 40(twice), 41, 47(twice), 48, 54(twice), 55, 61(twice), 62, 75(twice), 76, 89(twice), 90, 103(twice), 104, 133(twcie), 134, 150(twice), 151
measure: Cardionat® levels in urine
timeFrame: following days 0, 22, 26, 33, 40(twice), 41, 47(twice), 48, 54(twice), 55, 61(twice), 62, 75(twice), 76, 89(twice), 90, 103(twice), 104, 133(twcie), 134, 150(twice), 151
measure: Exercise load duration (Tel)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: Time of onset of aerobic threshold (Tat)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: Time of onset of the anaerobic threshold (Tant)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: Respiratory quotient (R)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: Maximum oxygen consumption (MOC)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: The level of oxygen consumption in the aerobic threshold (V'O2AT)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: The level of oxygen consumption in the anaerobic threshold (V'O2ANT)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
measure: Heart rate (HR)
timeFrame: following days 22, 26, 33, 40, 41, 47, 48, 54, 55, 61, 62, 75, 76, 89, 90, 103, 104, 133, 134, 150, 151
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "State Scientific Center of Russian Federation - the Federal Medical Biophysical Center named after A I Burnazyan" (FSBI SSC FMBC name AI Burnazyan FMBA of Russia)
Study officials:
References:
citation: Rabin O, Uiba V, Miroshnikova Y, Zabelin M, Samoylov A, Karkischenko V, Semyonov S, Astrelina T, Razinkin S. Meldonium long-term excretion period and pharmacokinetics in blood and urine of healthy athlete volunteers. Drug Test Anal. 2019 Apr;11(4):554-566. doi: 10.1002/dta.2521. Epub 2018 Nov 12.