Study of the Tolerability and Pharmacokinetic of ZL-2102 With an Investigation of Food Effect in Healthy Male Subjects

January 22, 2019 updated by: Zai Lab Pty. Ltd.

Randomized, Double-blind, Placebo-controlled Study of the Tolerability and Pharmacokinetics of Ascending Single and 14-day Repeated Oral Doses of ZL-2102 With a Pilot Investigation of Food Effect in Healthy Male Subjects

The first-in-man study are designed as below to assess safety, tolerability, and preliminary pharmacokinetics of ZL-2102.

  • Double-blind randomized, placebo-controlled ascending single oral doses (Part 1, ZL-2102-SAD);
  • Open-label, randomized, 2-sequence, 2-period, 2-treatment crossover (Part 2, ZL-2102-FED);
  • Double-blind randomized, placebo-controlled, ascending repeated oral doses for 14 days (Part 3, ZL-2102-MAD).

A total of 104 subjects will be enrolled.

Study Overview

Status

Status

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

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

There are 3 parts to the study. Subjects will be randomized to receive ZL-2102 or matching placebo (3: 1 ratio) in Parts 1 and Part 3 of the study. Subjects in Part 2 will be randomized 1:1 to receive ZL-2102 in each possible treatment sequence (fed/fasted or fasted/fed).

In Part 1 (ZL-2102-SAD), the safety, tolerability and pharmacokinetics of the study drug or placebo will be tested after a single dose in the form of a capsule when given after an overnight fast. There will be 7 groups. Groups 1 to 7 will have a total of 8 participants in each group, with 56 participants total in all 7 groups. Each group will receive a different dose of the study drug or placebo in the following order of strength: 5, 20, 60, 150, 300, 500, 750 mg. Plasma samples will be collected in 0H,0H30M,1H,2H,3H,4H,5H,6H,8H,10H,12H,16H,24H,48H and on Day 8. Urine samples will be collected at 0-4,4-8,8-12,12-24,24-28H intervals. Subjects will be confined to the unit for 3 days and the follow-up observation period is 7 days after the administration.

Part 2 of the study (ZL-2102-FED) will test the effect of a high-fat meal on safety, tolerability and pharmacokinetics of the study drug after a single dose in 12 healthy male subjects. Choice of dose of ZL-2102 will be made based on review of the blinded preliminary safety, tolerability and pharmacokinetics data in Part 1. No subjects will receive placebo in Part 2. Two single doses separated by at least a 7-day wash-out period. One dose will be given under fed (standardized high-fat breakfast) and one will be under fasted conditions.

Part 3 of the study (ZL-2102-MAD) will test the safety, tolerability and pharmacokinetics of the study drug after repeated doses of the study drug. Three dose level groups (9 active and 3 placebo) with 12 healthy male subjects will be enrolled.Choice of the actual daily ZL-2102 doses will be made based upon a review of the blinded preliminary safety, tolerability, and pharmacokinetics data in Part 1. Three ascending once-daily repeated doses of ZL-2102 or placebo for 14 days or, alternatively, twice daily for 14 days if indicated by pharmacokinetics parameters from Part 1 (ZL-2102-SAD). If the dose needs to be twice daily, the total daily doses will be given half in the morning and half in the evening 12 hours later. Dose will be administered either under fed or fasted conditions depending on blinded Part 2 (ZL-2102-FED) results.

The trial will be conducted in Linear Clinical Research Ltd.by Principle Investigator Janakan Krishnarajah,MD and his team.

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.
120

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

  • Australia
      • Perth, Australia
        • Linear Clinical Research Unit

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 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Male subject, between 18 and 45 years of age inclusive.
  • Body weight between 50.0 and 100.0 kg inclusive, body mass index (BMI) between 18.0 and 30.0 kg/m² inclusive.
  • Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
  • Normal vital signs after 5 minutes resting in a semi recumbent position.
  • Normal standard 12-lead ECG after 5 minutes resting in a semi recumbent position.
  • Laboratory parameters within the normal range, or considered not clinically significant by the Investigator.
  • Subject returns a negative result to the Serology,Urine drug screen and alcohol breath tests.
  • Having given written informed consent prior to any procedure related to the study.
  • Not under any administrative or legal supervision.
  • Males must agree to use adequate contraception for the duration of the study and for 3 months post completion of dosing.

  • Subject agrees to the following study restrictions:

    1. Subject will not consume citrus fruits and their juices for 5 days before the start of the study, and for the duration of the study.
    2. Subject will not consume alcohol, tea, coffee, chocolate, quinine or caffeine-containing beverages from Day 1 and for the duration of the study.
    3. Subject will note smoke or use tobacco from Day 1 and for the duration of the study.
    4. Subject will avoid intensive physical activity from Day 1 and for the duration of the study.

Exclusion Criteria:

  • Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteo-muscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
  • Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
  • Blood donation, any volume, within 2 months prior to Screening.
  • Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined by a decrease in systolic blood pressure ≥ 20 mmHg within 3 minutes when changing from the supine to the standing position.
  • Presence or history of drug hypersensitivity, or allergic disease (excluding hay fever) diagnosed and treated by a physician.
  • History or presence of drug or alcohol abuse (alcohol consumption >40 grams per day).
  • Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during the study.
  • Excessive consumption of beverages with xanthine bases (>4 cups or glasses per day).
  • Any prescription medication within 14 days and any over the counter medication within 7 days before Screening or within 5 times the elimination half-life or Pharmacodynamic half-life of that drug whichever is longest unless approved by both the Investigator and the Medical Monitor; any vaccination within the last 28 days. If necessary, paracetamol (acetaminophen) may be administered with the approval of the Investigator.
  • Any subject who, in the judgment of the Investigator, is likely to be non-compliant during the study, or unable to cooperate because of a language problem or poor mental development.
  • Receipt of any investigational study drug within 30 days prior to screening.
  • Any subject who is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in the conduct of the protocol.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

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.
Active Comparator: ZL-2102
Planned to be administrated in an ascending manner: 5,20,60,150,300,500,750mg
Drug: ZL-2102
A selective and reversible inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS).
Placebo Comparator: Placebo
Placebo matching ZL-2102
Drug: Placebo matching ZL-2102

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
Time Frame
Part1,ZL-2102-SAD: Safety as measured by Adverse Events
Time Frame: 8 days
8 days
Part2,ZL-2102-FED: Safety as measured by Adverse Events
Time Frame: 15 days
15 days
Part3,ZL-2102-MAD: Safety as measured by Adverse Events
Time Frame: 21 days
21 days
Peak Plasma Concentration (Cmax) of ZL-2102
Time Frame: 48 hours
48 hours
Area under the plasma concentration versus time curve (AUC) of ZL-2102
Time Frame: 48 hours
48 hours

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
Time Frame
Part1,ZL-2102-SAD: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.
Time Frame: 8 days
8 days
Part2,ZL-2102-FED: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.
Time Frame: 15 days
15 days
Part3,ZL-2102-MAD: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.
Time Frame: 21 days
21 days

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
Time Frame
Peak Urine Concentration (Cmax) of ZL-2102
Time Frame: 48 hours
48 hours
Area under the urine concentration versus time curve (AUC) of ZL-2102
Time Frame: 48 hours
48 hours
Part3,ZL-2102-MAD: Concentration of 2,3-dinor-6-keto-PGF1α as Prostaglandin I2 metabolite in urine.
Time Frame: 48 hours
48 hours
Part3,ZL-2102-MAD: Concentration of 13,14-dihydro-15-keto PGA2 and 13,14-dihydro-15-keto PGE2 as Prostaglandin E2 metabolite in urine.
Time Frame: 48 hours
48 hours
Part3,ZL-2102-MAD: Concentration of 11-dehydrothromboxane B2 as Thromboxane A2 metabolite in urine.
Time Frame: 48 hours
48 hours
Part3,ZL-2102-MAD: Concentration of 13, 14-dihydro-15-keto PGF2a as Prostaglandin F2α in plasma.
Time Frame: 48 hours
48 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.
Zai Lab Pty. Ltd.

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.
March 1, 2015

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.
April 1, 2016

Study Completion (Anticipated)

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.
August 1, 2019

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).
February 27, 2015

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.
March 17, 2015

First Posted (Estimate)

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.
March 24, 2015

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.
January 24, 2019

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.
January 22, 2019

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.
January 1, 2019

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.
  • ZL-2102-SAD/FED/MAD

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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