A Phase 1, Single-site, Open-label Study to Determine the Safety and Tolerability of Single and Multiple Doses of Intranasally Administered LMN-301 in Healthy Volunteers

Changes From Baseline of Oral Temperature.

时间窗: In part A vital signs are measured on Days 1 (4 timepoints), 2, 8 and 14. In part B vital signs are measured on Days 1 (3 timepoints), 3 or 4, 7, 10 or 11, 14 and 28.

Changes from baseline for oral temperature will be summarized at each scheduled timepoint using descriptive statistics.

Changes From Baseline of Respiratory Rate.

时间窗: In part A respiratory rate is measured on Days 1 (4 timepoints), 2, 8 and 14. In part B vital signs are measured on Days 1 (3 timepoints), 3 or 4, 7, 10 or 11, 14 and 28.

Changes from baseline for respiratory rate will be summarized at each scheduled timepoint using descriptive statistics.

Change From Baseline in Alanine Transaminase.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like alanine transaminase. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in Asparate Aminotransferase.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like asparate aminotransferase. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in Gamma Glutamyl Transferase.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like gamma glutamyl transferase. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in Bilirubin.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like bilirubin. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Changes From Baseline of Systolic and Diastolic Blood Pressure.

时间窗: In part A vital signs are measured on Days 1 (4 timepoints), 2, 8 and 14. In part B vital signs are measured on Days 1 (3 timepoints), 3 or 4, 7, 10 or 11, 14 and 28.

Changes from baseline for systolic and diastolic blood pressure will be summarized at each scheduled timepoint using descriptive statistics.

Changes From Baseline of Pulse Rate.

时间窗: In part A vital signs are measured on Days 1 (4 timepoints), 2, 8 and 14. In part B vital signs are measured on Days 1 (3 timepoints), 3 or 4, 7, 10 or 11, 14 and 28.

Changes from baseline for pulse rate will be summarized at each scheduled timepoint using descriptive statistics.

Changes From Baseline of Hemoglobin.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like hemoglobin. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Changes From Baseline of Single RR Heart Rate (Beats/Min).

时间窗: Change from baseline to Day 14 for the Sentinel Cohort (Part A), and change from baseline to Day 28 for the Main Cohort (Part B).

The following ECG parameters will be analyzed: single RR heart rate (beats/min). Observed values and changes from baseline for single RR heart rate (beats/min). will be summarized at each scheduled timepoint using descriptive statistics.

Changes From Baseline of Hematocrit.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures such as hematocrit. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in Neutrophils.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like neutrophils. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in Urea.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like urea. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Changes From Baseline of QRS Duration, Single Beat (ms).

时间窗: Change from baseline to Day 14 for the Sentinel Cohort (Part A), and change from baseline to Day 28 for the Main Cohort (Part B).

The following ECG parameters will be analyzed: QRS duration, single beat (ms). Observed values and changes from baseline for ECG parameters will be summarized at each scheduled timepoint using descriptive statistics.

Number of Participants With Adverse Events

时间窗: Daily for 28 days

All adverse events (AEs) will be coded using the latest version of MedDRA by system organ class (SOC) and preferred term, classified from verbatim terms. The number of treatment-emergent AEs (TEAEs) as well as the number and percentage of participants with at least one TEAE, will be summarized by SOC and preferred term. Summaries of TEAEs by severity as assessed by CTCAE v5.0 and relationship will also be presented. Summaries will also be presented for serious adverse events (SAEs), TEAEs leading to death or study withdrawal. The duration of all AEs will be determined and included in the listings. Solicited and unsolicited TEAEs will be summarized separately.

Change From Baseline in Creatinine.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like creatinine. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in Lactate Dehydrogenase.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like lactate dehydrogenase. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in PR Interval, Single Beat (ms).

时间窗: Change from baseline to Day 14 for the Sentinel Cohort (Part A), and change from baseline to Day 28 for the Main Cohort (Part B).

The following ECG parameters will be analyzed: PR interval (ms). Observed values and changes from baseline for ECG parameters will be summarized at each scheduled timepoint using descriptive statistics.

Number of Participants Discontinuing From the Study

时间窗: For 28 days after the first dose of LMN-301

The endpoint is the number of participants discontinuing from the study.

Change From Baseline in Platelets (10^9/L)

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures such as platelets. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline of Alkaline Phosphatase.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures such as alkaline phosphatase. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline of Prothrombin Intl. Normalized Ratio.

时间窗: For Part A on Days 2, 8 and 14 and For Part B on Days 3 or 4, 7, 14 and 28

Clinical laboratory safety data will be summarized by laboratory measures like prothrombin intl. normalized ratio. Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. The clinical assessment of laboratory data will be summarized at each scheduled timepoint using participant counts and percentages. Individual participant profiles will be presented for any laboratory parameters with at least one post-dose value outside the laboratory's reference ranges that is deemed clinically significant.

Change From Baseline in QTcB Interval, Single-beat (ms)

时间窗: Change from baseline to Day 14 for the Sentinel Cohort (Part A), and change from baseline to Day 28 for the Main Cohort (Part B).

The following ECG parameters will be analyzed: QTcB Interval. Observed values and changes from baseline for ECG parameters will be summarized at each scheduled timepoint using descriptive statistics.

Changes From Baseline Nasal Symptoms Using the Sino-Nasal Outcome Test (Total Score)

时间窗: For Part A Days 1 and 8. For Part B Days 1, 7, 14 and 28

The sino-nasal outcome test (SNOT-22) is to measure the consequences of rhinosinusitis. Scores will be totaled for all 22 items. The minimum score on the sinonasal outcome test-22 (SNOT-22) is 0 and the maximum score is 110. Changes from baseline in individual total sinonasal outcome test-22 (SNOT-22) scores will be calculated as the post-baseline value minus the baseline value. Thus, a negative change will reflect an improvement in the corresponding score. Observed values and changes from baseline will be summarized at each scheduled timepoint by treatment using descriptive statistics and tabulated for each cohort (dose level) and overall. Individual symptoms will be listed, with the 5 most important issues flagged. The total SNOT score will also be included in the listing.

Change From Baseline in QTcF Interval (ms).

时间窗: Change from baseline to end of study.

The following ECG parameters will be analyzed: QTcF Interval (ms). Observed values and changes from baseline for ECG parameters will be summarized at each scheduled timepoint using descriptive statistics. For QTcF Interval, the number of participants with values greater than 450 (and 480, 500) msec or an increase from baseline of at least 30 (and 60) msec will also be tabulated, in accordance with International Conference of Harmonization (ICH) E14