Bioequivalence Study of Sotalol, Tablets, 160 mg (Pharmtechnology LLC, Belarus), and Sotalex ®, Tablets, 160 mg (Bristol-Myers Squibb GmbH & Co. KGaA, Germany), in Healthy Volunteers Under Fasting Conditions

NCT03799536 | Completed Phase 1

• 1 other identifier: BE-SOTL-160- 2018
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, single-center, single-dose, two-treatment, two-sequence, two-period, crossover, comparative study, where each subject was randomly assigned to the reference or the test formulation in each period of the study (sequences RT or TR), in order to evaluate if both formulations are bioequivalent.The study was conducted in multiple groups.

Conditions

Bioequivalence

Keywords

Bioequivalence; Sotalol; Sotalex

Outcome Measures

Primary Outcomes (2)

• Cmax of sotalol for the test and the reference products

  Maximum concentration in plasma among observed concentrations at pre-specified time points

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

• AUC0-t of sotalol for the test and the reference products

  Area under the plasma concentration versus time curve from time 0 to the last measured concentration

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

Secondary Outcomes (6)

• AUC0-∞ of sotalol for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

• Tmax of sotalol for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

• T1/2 of sotalol for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

• Kel of sotalol for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

• AUCresid of sotalol for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 6; 8; 10; 12; 16; 24; 36; 48; 72 hours after dosing

Study Arms (2)

Sequence AB

EXPERIMENTAL

Subjects assigned to sequence AB will receive a single 160 mg dose of the test product Sotalol (1 x 160 mg tablet) marked as A in the sequence in the period 1 and a single 160 mg dose of the reference product Sotalex (1 x 160 mg tablet) marked as B in the sequence in the period 2 . These treatments will be administered orally with approximately 200 mL of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Sotalol

Sequence BA

ACTIVE COMPARATOR

Subjects assigned to sequence BA will receive a single 160 mg dose of the reference product Sotalex (1 x 160 mg tablet) marked as B in the sequence in the period 1 and a single 160 mg dose of the test product Sotalol (1 x 160 mg tablet) marked as A in the sequence in the period 2 . These treatments will be administered orally with approximately 200 mL of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Sotalex

Interventions

Sotalol DRUG

Sotalol, Tablets,160 mg, manufactured by Pharmtechnology LLC, Belarus

Also known as: the test product

Sequence AB

Sotalex DRUG

Sotalex, Tablets,160 mg, manufactured by Bristol-Myers Squibb GmbH \& Co. KGaA, Germany

Also known as: the reference product

Sequence BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Caucasian men or women aged between 18 to 55 years
• Body mass index 18.5-30 kg/m²
• Subjects who have no signs of disease during the screening, and whose screening is conducted within 21 days after the registration in the trial
• Subjects whose laboratory blood and urine values are within the normal range orof deviations are considered by researchers to be clinically insignificant
• Non-smokers or ex-smokers (defined as completely quitting smoking for at least three months prior to being included in the test)
• No known history of alcohol abuse
• No known history of abuse of drugs (benzodiazepines, opioids, cocaine, barbiturates, amphetamine, etc.)
• Willingness to comply with the protocol requirements regarding the restriction of the consumption of products containing xanthine (coffee, tea, chocolate, cola, etc.) for at least 48 hours and products containing tobacco, alcohol-containing products and beverages, grapefruit and/or its juice, food containing poppy at least 72 hours prior taking the investigational medicinal products and over the course of the study, as well as requirements regarding the intake of food, fluids and physical activity imposed by the study
• Healthy subject according to medical history, physical examination and assessment of basic vital signs
• No significant abnormalities on 12-lead ECG
• No significant abnormalities on the chest x-ray obtained within 12 months prior the start of the study
• Consent of women of childbearing age and male participants to use medically confirmed barrier methods of contraception (from the date of screening to the completion of the study), or surgical sterilization in history, or women in postmenopause (at least 24 months) or hysterectomy in history . If women use hormonal contraceptives,they should stop them at least 60 days prior the planned beginning of the study
• The subject's voluntary willingness to provide written informed consent
• The ability, at disceretion of the researcher, to follow all the requirements of the protocol
• The ability, at judgment of the researcher, to follow all the requirements of the protocol

You may not qualify if:

• Known history of allergy
• Known contraindications to the use of investigational products or hypersensitivity to the active substance or components of drugs
• Use of drugs with enzymatic-modifying activity, within 28 days prior the beginning of the study
• Use any over-the-counter or prescription drugs (including vitamins, minerals, herbal remedies, and dietary supplements) within 14 days prior the administration of investigational products and over the course of the study
• Intense physical exercises within 24 hours prior to the administration of investigational products
• Any medical or surgical interventions that can disrupt the function of the hematopoietic system, the gastrointestinal tract (with the exception of appendectomy), the liver, urinary system and other body systems
• Any chronic diseases or conditions of the urinary, cardiovascular, neuroendocrine, immune, central nervous systems, hematopoietic system, gastrointestinal tract, liver, organs of vision and other systems of the body and diabetes in medical history, mental illness in an active phase or the history
• The presence of any hereditary disease
• Participation in any clinical trials within 90 days prior the beginning of the current clincial study
• Oncological diseaes in medical history
• Any blood donation within 90 days prior the beginning of the current clincial study
• Acute infectious diseases within 28 days prior the beginning of the current clincial study as well as positive testing for HIV, hepatitis B and C, and syphilis
• Positive test for alcohol
• Positive urinary screen test for drugs of abuse
• Swallowing problems in mediical history

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• National Anti-Doping Labaratory: collaborator

Study Sites (1)

National Anti-Doping Laboratory

Settl.Lesnoy, Minsk Oblast, 223040, Belarus

Location

MeSH Terms

Interventions

Sotalol

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Anastasia Teteryukova, MD

  National Anti-Doping Labaratory

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The subjects and the investigator will not be blinded towards the identity of the study products. However, analysts will be blinded towards identity of the study products administered.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 10, 2019
• Study Start: January 9, 2019
• Primary Completion: February 4, 2019
• Study Completion: February 11, 2019
• Last Updated: June 7, 2019

Record last verified: 2019-01

Locations

BE (1)