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A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Nebulized Ensifentrine in Healthy Chinese Subjects

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Ensifentrine
Ensifentrine
Sponsored by
Nuance Pharma (shanghai) Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria: Subjects (18-50 yrs) who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG without abnormality or with abnormality of no clinical significance; A male subject must agree to use contraception as detailed in the protocol from the screening visit to within 30 days of the last dose after study completion and refrain from donating sperm during this period; Subjects never smoke or is ex-smoker for ≥ 12 months,never chewing tobacco within 90 days prior to screening; 3. Body weight must be ≥ 50 kg and body mass index (BMI) between 18.0 and 30.0 kg/m2. Exclusion Criteria: History or current malignancy of any organ system, treated or untreated within the past 5 years; Known allergy, immune reaction, or intolerance to ensifentrine or any of the excipients of the formulation and/or ineligible to receive ensifentrine; Subjects with the history of pulmonary and cardiovascular disease; Any chronic condition or disease, including but not limited to: Metabolism, endocrine (such as diabetes, hypothyroidism/hyperthyroidism), liver, kidney, gastrointestinal tract, hematology or nervous system and other diseases; Respiratory tract infection (upper and/or lower) treated with antibiotics within 12 weeks of screening visit; Current infection of clinical significance or known ongoing inflammatory condition; Live or attenuated vaccine(s) within 1 month prior to screening, or plan to receive such vaccines during the study; Immunotherapy within 30 days of screening; Subjects who participated in any other interventional clinical trials within 3 months prior to screening; Subjects who have used any drugs that inhibit or induce liver metabolism of drugs within 30 days prior to screening or have used any drugs within 14 days prior to screening; Subjects who have a history of alcohol or drug abuse, or have used any drug abuse within 6 months before screening; Subjects with a positive alcohol breath test, or a positive urinalysis screening test or a positive smoke test; Creatinine clearance < 80mL/min by Cockcroft-Gault formula; Subjects who have clinically significant abnormalities in physical examination, vital signs, chest x-ray, and laboratory examinations; Pulmonary function test: Subjects who have measured value of forced expiratory volume in first second (FEV1) / predicted value of FEV1 ≤ 80% or forced vital capacity (FVC) ≤ 80% of predicted value or any other clinically significant abnormality; Subjects who have any of abnormal findings in 12-lead ECG or any other clinically significant abnormality; Subjects who have undergone surgery within 6 months prior to the dosing of the study drug or who have undergone surgery within 4 weeks prior to the dosing of the study drug or who plan to undergo surgery during the trial; Donated blood or blood products or had substantial loss of blood (more than 300 mL) within 56 days prior to the first administration of study treatment. Unwilling to follow the lifestyle considerations; Any other reason that the investigator considers the patient unsuitable to participate in the study.

Sites / Locations

  • The Third Hospital of Changsha

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

Subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID).

Subjects will receive two single doses of 1.5 mg and 6 mg ensifentrine, separated by at least a 7-day washout period using crossover design.

Outcomes

Primary Outcome Measures

Cmax of RPL554
Blood PK sampling for RPL554 concentration
AUC0-t of RPL554
Area under the plasma concentration from time 0 to the last collection time after drug administration
Tmax of RPL554
Time to maximum observed plasma concentration
t1/2 of RPL554
Half-life of RPL554

Secondary Outcome Measures

Adverse events
Adverse events

Full Information

First Posted
February 14, 2023
Last Updated
April 20, 2023
Sponsor
Nuance Pharma (shanghai) Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05758428
Brief Title
A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Nebulized Ensifentrine in Healthy Chinese Subjects
Official Title
A Phase 1, Open-Label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Nebulized Ensifentrine in Healthy Chinese Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
March 6, 2023 (Actual)
Primary Completion Date
April 18, 2023 (Actual)
Study Completion Date
April 18, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nuance Pharma (shanghai) Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a phase 1, open-label, parallel cohort study to evaluate the PK, safety and tolerability of nebulized ensifentrine following administration of single and multiple doses in healthy Chinese male subjects.
Detailed Description
This study consists of two cohorts, and approximately a total of up to 28 healthy male subjects, 14 subjects in Cohort 1, and 14 subjects in Cohort 2, will be enrolled. Cohort 2 will be randomly assigned to Sequence 1 and Sequence 2 according to the ratio of 1:1. Treatment Group Cohort 1: subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID). Cohort 2: subjects will receive two single doses of 1.5 mg and 6 mg ensifentrine, separated by at least a 7-day washout period using crossover design.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID).
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Subjects will receive two single doses of 1.5 mg and 6 mg ensifentrine, separated by at least a 7-day washout period using crossover design.
Intervention Type
Drug
Intervention Name(s)
Ensifentrine
Intervention Description
14 Subjects enrolled will use one 3 mg/2.5 mL ampule for the 3 mg dose, subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID). On the dosing day (Day 1), subjects will receive a single dose of 3 mg ensifentrine. On Day 4, subjects will receive multiple doses of 3 mg ensifentrine BID for 3 days (Day 4 to Day 6), and a morning dose will be administered on Day 7.
Intervention Type
Drug
Intervention Name(s)
Ensifentrine
Other Intervention Name(s)
Placebo
Intervention Description
14 subjects will be enrolled in this cohort, then randomly assigned to one of 2 treatment sequences (6mg and 1.5mg single dose). Subjects will 2 different dose levels of study drug. Two 3 mg/2.5 mL ampules will be needed for the 6 mg dose (5 mL total volume) and the 1.5 mg dose will be achieved using an appropriate dilution protocol described in the pharmacy manual.
Primary Outcome Measure Information:
Title
Cmax of RPL554
Description
Blood PK sampling for RPL554 concentration
Time Frame
0 to 72 hours
Title
AUC0-t of RPL554
Description
Area under the plasma concentration from time 0 to the last collection time after drug administration
Time Frame
0 to 72 hours
Title
Tmax of RPL554
Description
Time to maximum observed plasma concentration
Time Frame
0 to 72 hours
Title
t1/2 of RPL554
Description
Half-life of RPL554
Time Frame
0 to 72 hours
Secondary Outcome Measure Information:
Title
Adverse events
Description
Adverse events
Time Frame
From the first dose usage to the end of the study, approxiamtely up to 15 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subjects (18-50 yrs) who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG without abnormality or with abnormality of no clinical significance; A male subject must agree to use contraception as detailed in the protocol from the screening visit to within 30 days of the last dose after study completion and refrain from donating sperm during this period; Subjects never smoke or is ex-smoker for ≥ 12 months,never chewing tobacco within 90 days prior to screening; 3. Body weight must be ≥ 50 kg and body mass index (BMI) between 18.0 and 30.0 kg/m2. Exclusion Criteria: History or current malignancy of any organ system, treated or untreated within the past 5 years; Known allergy, immune reaction, or intolerance to ensifentrine or any of the excipients of the formulation and/or ineligible to receive ensifentrine; Subjects with the history of pulmonary and cardiovascular disease; Any chronic condition or disease, including but not limited to: Metabolism, endocrine (such as diabetes, hypothyroidism/hyperthyroidism), liver, kidney, gastrointestinal tract, hematology or nervous system and other diseases; Respiratory tract infection (upper and/or lower) treated with antibiotics within 12 weeks of screening visit; Current infection of clinical significance or known ongoing inflammatory condition; Live or attenuated vaccine(s) within 1 month prior to screening, or plan to receive such vaccines during the study; Immunotherapy within 30 days of screening; Subjects who participated in any other interventional clinical trials within 3 months prior to screening; Subjects who have used any drugs that inhibit or induce liver metabolism of drugs within 30 days prior to screening or have used any drugs within 14 days prior to screening; Subjects who have a history of alcohol or drug abuse, or have used any drug abuse within 6 months before screening; Subjects with a positive alcohol breath test, or a positive urinalysis screening test or a positive smoke test; Creatinine clearance < 80mL/min by Cockcroft-Gault formula; Subjects who have clinically significant abnormalities in physical examination, vital signs, chest x-ray, and laboratory examinations; Pulmonary function test: Subjects who have measured value of forced expiratory volume in first second (FEV1) / predicted value of FEV1 ≤ 80% or forced vital capacity (FVC) ≤ 80% of predicted value or any other clinically significant abnormality; Subjects who have any of abnormal findings in 12-lead ECG or any other clinically significant abnormality; Subjects who have undergone surgery within 6 months prior to the dosing of the study drug or who have undergone surgery within 4 weeks prior to the dosing of the study drug or who plan to undergo surgery during the trial; Donated blood or blood products or had substantial loss of blood (more than 300 mL) within 56 days prior to the first administration of study treatment. Unwilling to follow the lifestyle considerations; Any other reason that the investigator considers the patient unsuitable to participate in the study.
Facility Information:
Facility Name
The Third Hospital of Changsha
City
Changsha
State/Province
Hunan
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Nebulized Ensifentrine in Healthy Chinese Subjects

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