Bioequivalence Study of Two Formulations of Propafenone 300 mg Film-coated Tablets in Healthy Adult Volunteers After a Single Oral Dose Administration Under Fasting Conditions

NCT03915340 | Completed Phase 1

• 1 other identifier: PTL-P4-227 (v. 2.0 04/09/2019)
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This bioequivalence study will be conducted in healthy male and female volunteers in order to determine the bioequivalence of two different formulations of propafenone after a single oral dose administration under fasting conditions.

Conditions

Bioequivalence

Keywords

propafenone; bioequivalence; Rytmonorm

Outcome Measures

Primary Outcomes (2)

• Cmax of propafenone in plasma after administration of the test and the reference products

  Maximum observed concentration in plasma

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

• AUC0-T of propafenone in plasma after administration of the test and the reference products

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

Secondary Outcomes (8)

• Tmax of propafenone in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

• TLQC of propafenone in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

• AUC0-∞ of propafenone in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

• Residual area of propafenone in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

• Time point where the log-linear elimination phase begins (TLIN) of propafenone in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00 hours after each drug administration

Study Arms (2)

Sequence ABAB

OTHER

16 subjects assigned to the sequence ABAB will receive a single 300 mg dose of the test product Propafenone (1 x 300 mg film-coated tablet), marked as A in the sequence, in Periods 1 and 3 and a single 300 mg dose of the reference product Rytmonorm (1 x 300 mg film-coated tablet), marked as B in the sequence, in periods 2 and 4. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a minimum of 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Propafenone; Drug: Rytmonorm

Sequence BABA

OTHER

16 subjects assigned to the sequence BABA will receive a single 300 mg dose of the reference product Rytmonorm (1 x 300 mg film-coated tablet), marked as B in the sequence, in Periods 1 and 3 and a single 300 mg dose of the test product Propafenone (1 x 300 mg film-coated tablet), marked as A in the sequence, in periods 2 and 4. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a minimum of 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Propafenone; Drug: Rytmonorm

Interventions

Propafenone DRUG

Propafenone is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 300 mg of propafenone hydrochloride.

Also known as: the test product

Sequence ABAB; Sequence BABA

Rytmonorm DRUG

Rytmonorm is manufactured by Famar Lyon, France (MAH: Mylan Healthcare GmbH, Germany). Each tablet contains 300 mg of propafenone hydrochloride.

Also known as: the reference product

Sequence ABAB; Sequence BABA

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form (ICF)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Healthy adult male or female volunteer
• A female volunteer must meet one of the following criteria:
• Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Systemic contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
• Intrauterine device (with or without hormones)
• Condom with intra-vaginally applied spermicide
• Participant whose partner has had a vasectomy less than 6 months prior to dosing, and agrees to use an additional acceptable method of contraception from the first study drug administration through to at least 30 days after the last dose of the study drug
• Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (i.e. at least 1 year without menses without an alternative medical condition prior to the first study drug administration)
• A male volunteer meeting one of the following criteria:
• Participant is able to procreate and agrees to use one of the accepted contraceptive regimens and not donate sperm from the first study drug administration to at least 90 days after the last drug administration. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository)

You may not qualify if:

• Females who are lactating at screening
• Females who are pregnant according to the pregnancy test at screening or prior to the first study drug administration
• Seated pulse rate less than 50 Beats per Minute (bpm) or more than 90 bpm at the screening visit or prior to the first study drug administration
• History of significant hypersensitivity to propafenone or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence of significant gastrointestinal, liver or kidney disease, or any other condition known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
• History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
• Presence of out-of-range cardiac interval (PR \< 110 msec, PR \> 200 msec, QRS \< 60 msec, QRS \>110 msec and QTc \> 440 msec) on the ECG at screening or other clinically significant ECG abnormalities, unless deemed non-significant by the investigator
• History of myasthenia gravis
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the 28 days prior to the first study drug administration
• Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of the investigator would put into question the status of the volunteer as healthy
• Any history of tuberculosis
• Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
• Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Altasciences Company Inc.

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

Propafenone

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Study Officials

• Eric Sicard, MD

  Altasciences Company Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The randomization code will not be available to the personnel of the bioanalytical facility until the bioanalytical tables have been finalized and audited by the Quality Assurance (QA) department.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There will be two sequences in the study: A-B-A-B and B-A-B-A, where A = the test product, B = the reference product (see detailed description of A and B items below).

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 16, 2019
• Study Start: March 23, 2019
• Primary Completion: May 8, 2019
• Study Completion: May 8, 2019
• Last Updated: June 6, 2019

Record last verified: 2019-04

Locations

CA (1)