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

• Sponsor: Nuance Pharma (shanghai) Co., Ltd (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05758428
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 6.1
• Patients Per Site Per Month: 4.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Ensifentrine; Drug: Ensifentrine	Phase 1

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

1. Cohort 1: subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID).

2. 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Feb 28, 2023
• Anticipated Primary Completion Date: Jun 1, 2023
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID).	Drug: Ensifentrine; 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.
Experimental: 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.	Drug: Ensifentrine; 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.; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Cmax of RPL554 [0 to 72 hours]

   Blood PK sampling for RPL554 concentration

2. AUC0-t of RPL554 [0 to 72 hours]

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

3. Tmax of RPL554 [0 to 72 hours]

   Time to maximum observed plasma concentration

4. t1/2 of RPL554 [0 to 72 hours]

   Half-life of RPL554

Secondary Outcome Measures

1. Adverse events [From the first dose usage to the end of the study, approxiamtely up to 15 days]

   Adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 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;

2. 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;

3. Subjects never smoke or is ex-smoker for ≥ 12 months,never chewing tobacco within 90 days prior to screening;

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

Exclusion Criteria:

1. History or current malignancy of any organ system, treated or untreated within the past 5 years;

2. Known allergy, immune reaction, or intolerance to ensifentrine or any of the excipients of the formulation and/or ineligible to receive ensifentrine;

3. Subjects with the history of pulmonary and cardiovascular disease;

4. 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;

5. Respiratory tract infection (upper and/or lower) treated with antibiotics within 12 weeks of screening visit;

6. Current infection of clinical significance or known ongoing inflammatory condition;

7. Live or attenuated vaccine(s) within 1 month prior to screening, or plan to receive such vaccines during the study;

8. Immunotherapy within 30 days of screening;

9. Subjects who participated in any other interventional clinical trials within 3 months prior to screening;

10. 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;

11. Subjects who have a history of alcohol or drug abuse, or have used any drug abuse within 6 months before screening;

12. Subjects with a positive alcohol breath test, or a positive urinalysis screening test or a positive smoke test;

13. Creatinine clearance < 80mL/min by Cockcroft-Gault formula;

14. Subjects who have clinically significant abnormalities in physical examination, vital signs, chest x-ray, and laboratory examinations;

15. 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;

16. Subjects who have any of abnormal findings in 12-lead ECG or any other clinically significant abnormality;

17. 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;

18. 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.

19. Unwilling to follow the lifestyle considerations;

20. Any other reason that the investigator considers the patient unsuitable to participate in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Third Hospital of Changsha	Changsha	Hunan	China

Sponsors and Collaborators

• Nuance Pharma (shanghai) Co., Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nuance Pharma (shanghai) Co., Ltd
• ClinicalTrials.gov Identifier: NCT05758428
• Other Study ID Numbers: RPL554-AHC001
• First Posted: Mar 7, 2023
• Last Update Posted: Mar 7, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

No Results Posted as of Mar 7, 2023