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

A Phase I, Prospective, Open Label, Multiple Dose Study Of ZYIL1 Administered Via Oral Route To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics In Healthy Adult 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: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ZYIL1 Capsule

Detailed Description

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

It will be conducted in up to 3 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 multiple oral dose of ZYIL1 from day 1 to till day 14.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• 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 venipuncture 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZYIL1; Capsule administration. Six subjects will be recruited in each cohort. safety data up to day 14 will be evaluated. Single dose will be administered in ascending manner starting from 12.5 mg.	Drug: ZYIL1 Capsule; NLRP3 inflammasome inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse event of ZYIL1 following a Multiple oral dose in healthy subjects	he Common Terminology Criteria for Adverse Event (CTCAE) (Version 5.0 or higher) system will be used for reporting and grading	Baseline to Day 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)	At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.	Day 1 to Day 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmin,ss	At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.	Day 1 to Day 16
Tmin,ss	At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.	Day 1 to Day 16
Cmax,ss	At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.	Day 1 to Day 16
% Fluctuation	At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.	Day 1 to Day 16
Accumulation Index	At each dose level, blood samples will be withdrawn for the evaluation of pharmacokinetic.	Day 1 to Day 16

Collaborators and Investigators

• Sponsor: Zydus Lifesciences Limited
• Investigators: Study Chair: Dr Deven Parmar, MD, Zydus Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): October 25, 2021

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: NLRP3; NLPR3 Inflammasone inhibitor
• Other Study ID Numbers: ZYIL1 1002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No