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

NCT05758428 | Completed Phase 1

• 1 other identifier: RPL554-AHC001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (4)

• Cmax of RPL554

  Blood PK sampling for RPL554 concentration

  0 to 72 hours

• AUC0-t of RPL554

  Area under the plasma concentration from time 0 to the last collection time after drug administration

  0 to 72 hours

• Tmax of RPL554

  Time to maximum observed plasma concentration

  0 to 72 hours

• t1/2 of RPL554

  Half-life of RPL554

  0 to 72 hours

Secondary Outcomes (1)

• Adverse events

  From the first dose usage to the end of the study, approxiamtely up to 15 days

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

Drug: Ensifentrine

Cohort 2

EXPERIMENTAL

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.

Drug: Ensifentrine

Interventions

Ensifentrine DRUG

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.

Cohort 1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• \. Body weight must be ≥ 50 kg and body mass index (BMI) between 18.0 and 30.0 kg/m2.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Nuance Pharma (shanghai) Co., Ltd: lead

Study Sites (1)

The Third Hospital of Changsha

Changsha, Hunan, China

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: March 7, 2023
• Study Start: March 6, 2023
• Primary Completion: April 18, 2023
• Study Completion: April 18, 2023
• Last Updated: April 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)