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

NCT02397005 | Unknown Phase 1 DMC

• 1 other identifier: ZL-2102-SAD/FED/MAD
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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);
• 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.

Conditions

Chronic Obstructive Pulmonary Disease; Asthma; Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (5)

• Part1,ZL-2102-SAD: Safety as measured by Adverse Events

  8 days

• Part2,ZL-2102-FED: Safety as measured by Adverse Events

  15 days

• Part3,ZL-2102-MAD: Safety as measured by Adverse Events

  21 days

• Peak Plasma Concentration (Cmax) of ZL-2102

  48 hours

• Area under the plasma concentration versus time curve (AUC) of ZL-2102

  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.

  8 days

• Part2,ZL-2102-FED: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.

  15 days

• Part3,ZL-2102-MAD: Safety as measured by Physical examination, body weight, hematology, biochemistry, urinalysis, vital signs and 12-lead ECG.

  21 days

Other Outcomes (6)

• Peak Urine Concentration (Cmax) of ZL-2102

  48 hours

• Area under the urine concentration versus time curve (AUC) of ZL-2102

  48 hours

• Part3,ZL-2102-MAD: Concentration of 2,3-dinor-6-keto-PGF1α as Prostaglandin I2 metabolite in urine.

  48 hours

Study Arms (2)

ZL-2102

ACTIVE COMPARATOR

Planned to be administrated in an ascending manner: 5,20,60,150,300,500,750mg

Drug: ZL-2102

Placebo

PLACEBO COMPARATOR

Placebo matching ZL-2102

Drug: Placebo matching ZL-2102

Interventions

ZL-2102 DRUG

A selective and reversible inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS).

ZL-2102

Placebo matching ZL-2102 DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zai Lab Pty. Ltd.: lead

Study Sites (1)

Linear Clinical Research Unit

Perth, Australia

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma; Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pulmonary Fibrosis; Lung Diseases, Interstitial

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 24, 2015
• Study Start: March 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: August 1, 2019
• Last Updated: January 24, 2019

Record last verified: 2019-01

Locations

AU (1)