Bioequivalence Study of Digoxin Tablet in Healthy Subjects

August 6, 2024 updated by: Xiangya Hospital of Central South University

An Open-label, Randomized, Single-dose (0.25mg), Four-period Fully Replicated Bioequivalence Study of Digoxin Tablet Under Fasted and Fed Conditions in Healthy Subjects

The study followed an open-label, randomized, single-dose (0.25mg), four-period full-replicate design encompassing both fasted and fed conditions. Subjects were randomized into two sequences, labeled as group A (TRTR) and group B (RTRT), for the four sessions. By the use of a random table produced by SAS statistical software, the individuals were assigned at random to administer a single-dose (0.25mg) of either the reference or the test formulation of digoxin tablets. During the fasted study phase, participants were randomly administered digoxin tablets after an overnight fast of a minimum of 10 hours, and fasting continued for 4 hours post dose. During the fed trial, subjects consumed a high-fat breakfast 30 minutes before administering digoxin tablets, which consisted of approximately 500 to 600 kcal of fat, 150 kcal of protein, and 250 kcal of carbohydrates, totaling around 800 to 1000 kcal calories. The breakfast must be finished within 30 minutes. Digoxin tablets were administered to each subject in a single dosage with 240 mL of water. Each subject was assigned equitably and at random to one of the two groups. A 14-day washout period was implemented between each period. In the fasted study, blood samples were collected at various time points: predose, 0.17, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after dosing. Similarly, in the fed study, blood samples were collected at predose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after dosing. Following collection, the samples underwent centrifugation at 1700g for 10 minutes at 4℃. The resulting supernatant was then divided into two aliquots and stored at -80℃ until further analysis was conducted. A validated high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was employed to assess the level of digoxin in plasma samples. The PK analysis of the plasma concentration-time curve was performed using a non-compartmental modeling method with Phoenix WinNonlin software version 8.2.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hunan
      • Changsha, Hunan, China, 410008
        • Xiangya Hospital Central South University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy Chinese adults aged no less than 18 years
  • A body mass index (BMI) falling within the range of 19.0 to 26.0 kg/m2, and a body weight of no less than 45kg for females and 50kg for males respectively.
  • All participants signed the informed consent form after receiving thorough information about the study protocol and agreed to adhere to it.

Exclusion Criteria:

  • Allergic to digoxin tablets and other digitalis preparations, or allergic to two or more drugs (or foods);
  • Subjects cannot follow a uniform diet ;
  • Subjects cannot tolerate venipuncture or have a history of dizziness with needles or blood;
  • Subjects with medical history of cardiovascular (e.g., ventricular fibrillation, sinus node block), liver, kidney, endocrine, digestive tract, hematological, respiratory, malignant tumor, mental disorder, or any of the above diseases judged by the investigators as clinically significant;
  • Subjects underwent major surgical procedures within 6 months before screening or planned to undergo surgery during the study, and those who underwent surgery affecting drug absorption, distribution, metabolism, or excretion (except appendicitis surgery);
  • Screening stage of physical examination, vital signs measurement, cardiogram, heart color to exceed, whole chest is slice examination, laboratory examination, blood routine, routine urine and blood biochemistry, blood coagulation function, thyroid function, blood/urine pregnancy (only female subjects), etc.), the researchers determine abnormal have clinical significance;
  • Creatinine clearance rate (Ccr) that is beyond the scope of 80 ~ 120 ml/min (including boundary value);
  • Clinically significant abnormal results of hepatitis B surface antigen, hepatitis C antibody, treponema pallidum antibody, or human immunodeficiency virus antibody;
  • Long-term (within 3 months before screening) excessive consumption (more than 8 cups per day, 1 cup =200mL) of tea, coffee, or caffeinated beverages; Or consuming any food or beverage (e.g., coffee, strong tea, chocolate, etc.) containing caffeine within 48 hours before the first dose of study medication;
  • Consuming any beverage or food containing grapefruit or other substances affecting drug absorption, distribution, metabolism, excretion, etc., within 48 hours before the first dose of medication;
  • Use of any medication known to interact with digoxin tablets within 4 weeks before screening;
  • Patients who used long-acting estrogen or progestin injection or implant within 6 months before the trial; Use of short-acting contraceptives within 30 days before the trial;
  • Subjects who had used any prescription drugs, over-the-counter drugs, herbal medicines, or health supplements within 14 days before the first study medication;
  • 3 months before the screening of daily smoking more than 5 pieces, and chosen to the whole experiments cannot accept ban smokers;
  • Positive alcohol breath test before first medication use or had consumed more than 14 standard units (SD) per week (1 SD containing 14g of alcohol) in the 6 months prior to screening;
  • Subjects who were positive in drug screening before the first drug use or had a history of drug abuse within 1 year before the test;
  • Pregnant or lactating women, and male (or their partner) or female subjects who plan to become pregnant throughout the trial and within 3 months after the end of the study;
  • Female subjects who had unprotected sex within 14 days before screening;
  • Subjects who participated in another clinical trial and took drugs within 3 months before the first dose of the study drug;
  • Subjects donating blood or blood loss ≥400mL within 3 months before the first dose of study medication, or planning to donate blood or blood components during the study or within 3 months after the end of the study;
  • The investigator believes that any circumstances may affect the provision of informed consent or compliance with the trial protocol, or that the participant's participation in the trial may affect the trial results or their safety.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: digoxin test drug
digoxin tablet, 0.25mg, single dose
Drug: Digoxin
Administer a single-dose (0.25mg) of either the reference or the test formulation of digoxin tablets.
Active Comparator: digoxin reference drug
digoxin tablet, 0.25mg, single dose
Drug: Digoxin
Administer a single-dose (0.25mg) of either the reference or the test formulation of digoxin tablets.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
plasma concentration in fasted study.
Time Frame: predose, 0.17, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours
plasma concentration-time curve
predose, 0.17, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours
plasma concentration in fed study.
Time Frame: predose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours
plasma concentration in fasted study.
predose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xiangya Hospital of Central South University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Pingsheng Xu, Doctor, Xiangya Hospital of Central South University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 5, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 23, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 23, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 6, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BTINT024-BE-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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