Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ZYIL1 Following Oral Administration in Healthy Volunteers

June 16, 2021 updated by: Zydus Lifesciences Limited

A Phase 1, Prospective Open Label, Single Dose, Single Arm Study of ZYIL1 Administered Via Oral Route to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Adult Human Subjects

ZYIL1 is a novel oral selective NLRP3 inflammasome inhibitor which prevents NLRP3-induced ASC oligomerization, thus inhibiting NLRP3 inflammasome pathway. ZYIL1 is expected to show benefit in patients demonstrating cytokine, like IL1β flare, including those exhibiting cytokine storm related to COVID-19 and other viral inflammatory diseases.

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.

Detailed Description

It is an open label, study designed to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) following a single-oral dose administration of ZYIL1 to healthy subjects aged between 18-55 years old (Both Inclusive).

It will be conducted in up to 7 cohorts of 6 subjects each. Each cohort will be enrolled within a 28 day screening period to ensure subjects meet all the inclusion criteria and none of the exclusion criteria. Subjects will be administered single oral dose of ZYIL1 on Day 1.

In this study each cohort containing six subjects will be given a single oral dose of ZYIL1 in ascending manner. Initially, up to 3 cohorts of 18 subjects will be enrolled and dosed. Interim analysis will be done after completion of three cohorts and submitted to Central Licensing Authority of India(CLA). Further cohorts (i.e. cohort S4 onwards) will be conducted after obtaining approval of CLA.

This is the first administration of ZYIL1 in humans; therefore, study design adjustments may be made based on emerging data from each dose cohort based on review of preliminary safety, tolerability, and PK results.

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.
30

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

  • India
    • Gujarat
      • Ahmedabad, Gujarat, India, 382213
        • Zydus Research Centre

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

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Healthy male or non-lactating non-pregnant female between 18 and 55 years of age at the time of signing the informed consent form (ICF). (Both inclusive).
  2. Body mass index of 18.5 to 30.0 kg/m2 (Both inclusive) with a body weight of 50 to 100 kg (Both inclusive).
  3. Normal QTc interval at screening and Check In [QTcF ≤450 ms]
  4. Male subjects must agree to use adequate contraception methods during the study and be willing and able to continue contraception for 90 days after administration of study treatment.
  5. Capable of giving written informed consent, which includes compliance with the study procedures, restrictions, and requirements listed in the protocol.
  6. Subjects who, in the opinion of the Investigator, are healthy as determined by their pre study medical history, clinical examination, 12-lead ECG and clinical laboratory tests within the institutional normal range or judged as not clinically significant by the Investigator, including the following parameters: hematology, serum biochemistry, urinalysis, and serology
  7. Female subjects with history of sterility or at least 1 year menopause or use of long acting non hormonal contraceptive measures (e.g., intrauterine device) and be willing and able to continue contraception for 90 days after administration of study treatment.

Exclusion Criteria:

  1. History or presence of alcoholism or drug abuse within the past 1 year.
  2. Presence or history of any of the following disorders/disease within the past 3 months, that might have impact on the clinical trial as per the investigator discretion: cardiovascular, cerebrovascular, dermatological, gastrointestinal, gynecological, hematological, hepatic, malignancy, metabolic, musculoskeletal, neurological, urological, psychiatric, renal, respiratory, venereal, any other major disorders
  3. History of clinically significant hypersensitivity, intolerance, or allergies, as determined by the Investigator.
  4. History of COVID-19 infection within 14 days or contact with a confirmed active COVID-19 positive patient within 14 days; or positive COVID-19 test within 5 days of Check-in. .
  5. History or presence of smoking or consumption of tobacco/nicotine products within the past 1 year.
  6. Difficulty with donating blood.
  7. Systolic blood pressure more than 140 mmHg or less than 100 mmHg or diastolic blood pressure more than 90 mmHg or less than 60 mmHg.
  8. Pulse rate less than 55/minute or more than 100/minute.
  9. Any clinically significant laboratory or ECG findings during screening
  10. Surgery within last 3 months or planned major surgery within next 3 months from the date of screening (other than minor cosmetic surgery and minor dental surgery).
  11. Subjects who have recent illness (eg, fever) within 14 days of check-in
  12. Volunteers who have participated in any drug research study within past 3 months.
  13. Volunteers who have donated one unit (350 ml) of blood in the past 3 months.
  14. Has used prescription drugs and other substances (eg, dietary or herbal supplements such as St John's Wort) known to be either significant enzyme inducers or enzyme inhibitors within 4 weeks of Day 1, or use of grapefruit or similar substances (Seville oranges or marmalade, grapefruit juice, grapefruit hybrids, pomelos, exotic citrus fruits or fruit juices) within 7 days of Day 1.
  15. Use of any over-the-counter (OTC), any prescription medications or alternative tradition of medicine (herbal medicines, homoeopathy, Siddha, Unani, etc.) within the 15 days or 5 half-lives (whichever is longer), prior to receiving study drug that might have impact on the clinical trial as per the investigator discretion.
  16. A positive urine drugs of abuse test or positive alcohol test at check-in.
  17. History of, or positive screening test for, hepatitis C infection (defined as positive for hepatitis C virus antibody), hepatitis B infection (defined as positive for hepatitis B surface antigen), or human immunodeficiency virus I or II.
  18. Any disorder that, in the Investigator's opinion, may interfere with study compliance, such as significant mental, nervous disorder or other illness. In making this assessment, the Investigator must refer to the study information provided including the Investigator's Brochure.
  19. Inability to be venipunctured or tolerate venous puncture.
  20. Any condition or abnormal baseline findings that in the Investigator's judgment might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to obtain the objective of the study.
  21. Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the subject unsuitable for the study.

  22. Female subjects who are pregnant, currently breastfeeding, or attempting to conceive.

    -

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: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

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: ZYIL1 Capsule
six subjects will be recruited in each cohort. safety data up to day 3 will be evaluated to determine whether progression to the subsequent dose Cohort is indicated. Single dose will be administered in ascending manner starting from 25 mg.
Drug: ZYIL1 capsule
NLRP3 inflammasome inhibitor

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
Incidence and Severity of Adverse event of ZYIL1 following a single oral dose in healthy subjects
Time Frame: Baseline to Day 3
The Common Terminology Criteria for Adverse Event (CTCAE) (Version 5.0 or higher) system will be used for reporting and grading
Baseline to Day 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to reach maximum plasma concentration (Tmax)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
Terminal half life (t1/2)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
Elimination rate constant (λz)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
Clearance (CL/F)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
Volume of distribution (Vd)
Time Frame: Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.
Predose; 0.5 hour; 1 hour; 1.5 hour; 2 hour; 3 hour; 4 hour; 5 hour, 6 hour; 8 hour; 12 hour, 24 hour and 48 hour
Amount recovered in Urine
Time Frame: Pre dose, 0-4 hours, 4-8 hours, 8-12 hours , 12-24 hours, 24-36 hours and 36 - 48 hours
Urine will be collected following IMP administrations on Day 1.The quantity of total urine collected at each time point will be recorded for calculating total urine output up to 48 hours.
Pre dose, 0-4 hours, 4-8 hours, 8-12 hours , 12-24 hours, 24-36 hours and 36 - 48 hours
Percent recovered in urine
Time Frame: Pre dose, 0-4 hours, 4-8 hours, 8-12 hours , 12-24 hours, 24-36 hours and 36 - 48 hours
Urine will be collected following IMP administrations on Day 1.The quantity of total urine collected at each time point will be recorded for calculating total urine output up to 48 hours.
Pre dose, 0-4 hours, 4-8 hours, 8-12 hours , 12-24 hours, 24-36 hours and 36 - 48 hours
Levels of IL-1β based on ex vivo LPS/ATP stimulation assay
Time Frame: Pre-dose, 3 hour, 6 hour, 12 hour and 24 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacodynamics
Pre-dose, 3 hour, 6 hour, 12 hour and 24 hour
Levels of IL-18 based on ex vivo LPS/ATP stimulation assay
Time Frame: Pre-dose, 3 hour, 6 hour, 12 hour and 24 hour
At each dose level, blood samples will be withdrawn for the evaluation of pharmacodynamics
Pre-dose, 3 hour, 6 hour, 12 hour and 24 hour

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.
Zydus Lifesciences Limited

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.
December 28, 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.
June 12, 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.
June 12, 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).
January 25, 2021

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.
January 28, 2021

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.
January 29, 2021

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.
June 18, 2021

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.
June 16, 2021

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.
December 1, 2020

More Information

Terms related to this study

Keywords

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.
  • ZYIL1 1001
  • CTRI/2020/12/030045 (REGISTRY: Clinical Trial Registry of India)

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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