Chronic Obstructive Pulmonary DiseasePhase 1NCT02397005
Study of the Tolerability and Pharmacokinetic of ZL-2102 With an Investigation of Food Effect in Healthy Male Subjects
A Phase 1 study testing ZL-2102 in people with Chronic Obstructive Pulmonary Disease and Asthma, run by Zai Lab Pty. Ltd. at 1 site in Australia.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease, Asthma, Idiopathic Pulmonary Fibrosis
- What is being tested?
- ZL-2102
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteAustralia
- Study dates
- Mar 2015to Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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:
- 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.
- Subject will not consume alcohol, tea, coffee, chocolate, quinine or caffeine-containing beverages from Day 1 and for the duration of the study.
- Subject will note smoke or use tobacco from Day 1 and for the duration of the study.
- Subject will avoid intensive physical activity from Day 1 and for the duration of the study.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- ZL-2102, Placebo matching ZL-2102
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Asthma, Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZL-2102Drug
A selective and reversible inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS).
Placebo matching ZL-2102Drug
| Study group | Role | What they receive |
|---|---|---|
| ZL-2102 | Active comparator | Planned to be administrated in an ascending manner: 5,20,60,150,300,500,750mg Receives: Drug: ZL-2102 |
| Placebo | Placebo comparator | Placebo matching ZL-2102 Receives: Drug: Placebo matching ZL-2102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part1,ZL-2102-SAD: Safety as measured by Adverse Events
Measured: 8 days
Part2,ZL-2102-FED: Safety as measured by Adverse Events
Measured: 15 days
Part3,ZL-2102-MAD: Safety as measured by Adverse Events
Measured: 21 days
Peak Plasma Concentration (Cmax) of ZL-2102
Measured: 48 hours
Area under the plasma concentration versus time curve (AUC) of ZL-2102
Measured: 48 hours
Secondary outcomes (3)
Part1,ZL-2102-SAD: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.
Measured: 8 days
Part2,ZL-2102-FED: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.
Measured: 15 days
Part3,ZL-2102-MAD: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionApr 2016
- Study completionAug 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zai Lab Pty. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02397005
- Sponsor's protocol ID
- ZL-2102-SAD/FED/MAD
- Status last verified
- Jan 2019
- First submitted
- 27 Feb 2015
- Last updated
- 24 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02397005
- Acronym / sponsor ID
- ZL-2102-SAD/FED/MAD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Zai Lab Pty. Ltd.Industry (pharma, biotech, devices)
- Study start
- Mar 2015 (actual)
- Primary completion
- Apr 2016 (actual)
- Study completion
- Aug 2019 (estimated)
- First posted
- 24 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZL-2102 | Active comparator | Drug: ZL-2102Planned to be administrated in an ascending manner: 5,20,60,150,300,500,750mg |
| Placebo | Placebo comparator | Drug: Placebo matching ZL-2102Placebo matching ZL-2102 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZL-2102A selective and reversible inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS). | Drug | ZL-2102 |
| Placebo matching ZL-2102 | Drug | Placebo |
Primary outcome
Part1,ZL-2102-SAD: Safety as measured by Adverse Events
Time frame: 8 days
Part2,ZL-2102-FED: Safety as measured by Adverse Events
Time frame: 15 days
Part3,ZL-2102-MAD: Safety as measured by Adverse Events
Time frame: 21 days
Peak Plasma Concentration (Cmax) of ZL-2102
Time frame: 48 hours
Area under the plasma concentration versus time curve (AUC) of ZL-2102
Time frame: 48 hours
3 secondary outcomes
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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZL-2102 in people with Chronic Obstructive Pulmonary Disease and Asthma, run by Zai Lab Pty. Ltd. at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part1,ZL-2102-SAD: Safety as measured by Adverse Events (time frame: 8 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2019.