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

NCT04731324 | Completed Phase 1

• 2 other identifiers: ZYIL1 1001CTRI/2020/12/030045
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

COVID 19; NLRP3; NLPR3 Inflammasone inhibitor

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Adverse event of ZYIL1 following a single oral dose in healthy subjects

  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 Outcomes (1)

• Maximum plasma concentration (Cmax)

  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 Outcomes (10)

• Time to reach maximum plasma concentration (Tmax)

  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)

  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)

  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

Study Arms (1)

ZYIL1 Capsule

EXPERIMENTAL

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

Interventions

ZYIL1 capsule DRUG

NLRP3 inflammasome inhibitor

ZYIL1 Capsule

Eligibility Criteria

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

You may qualify if:

• 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).
• Body mass index of 18.5 to 30.0 kg/m2 (Both inclusive) with a body weight of 50 to 100 kg (Both inclusive).
• Normal QTc interval at screening and Check In \[QTcF ≤450 ms\]
• 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.
• Capable of giving written informed consent, which includes compliance with the study procedures, restrictions, and requirements listed in the protocol.
• 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
• 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.

You may not qualify if:

• History or presence of alcoholism or drug abuse within the past 1 year.
• 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
• History of clinically significant hypersensitivity, intolerance, or allergies, as determined by the Investigator.
• 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. .
• History or presence of smoking or consumption of tobacco/nicotine products within the past 1 year.
• Difficulty with donating blood.
• 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.
• Pulse rate less than 55/minute or more than 100/minute.
• Any clinically significant laboratory or ECG findings during screening
• 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).
• Subjects who have recent illness (eg, fever) within 14 days of check-in
• Volunteers who have participated in any drug research study within past 3 months.
• Volunteers who have donated one unit (350 ml) of blood in the past 3 months.
• 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.
• 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.

Sponsors & Collaborators

• Zydus Lifesciences Limited: lead

Study Sites (1)

Zydus Research Centre

Ahmedabad, Gujarat, 382213, India

Location

Related Publications (1)

• Parmar DV, Kansagra KA, Momin T, Patel HB, Jansari GA, Bhavsar J, Shah C, Patel JM, Ghoghari A, Barot A, Sharma B, Viswanathan K, Patel HV, Jain MR. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral NLRP3 Inflammasome Inhibitor ZYIL1: First-in-Human Phase 1 Studies (Single Ascending Dose and Multiple Ascending Dose). Clin Pharmacol Drug Dev. 2023 Feb;12(2):202-211. doi: 10.1002/cpdd.1162. Epub 2022 Sep 5.

  PMID: 36065092 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

ZYIL1

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Dr Deven Parmar, MD

  Cadila Healthcare Ltd.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A phase 1, prospective open label, single dose, single arm study

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 29, 2021
• Study Start: December 28, 2020
• Primary Completion: June 12, 2021
• Study Completion: June 12, 2021
• Last Updated: June 18, 2021

Record last verified: 2020-12

Locations

IN (1)