Clinical trial NCT06217952: Safety, Tolerability, and Pharmacokinetics of SPL84 in Healthy Volunteers
Official title: A Phase 1, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of SPL84
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: SpliSense Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This Phase 1 study evaluated the safety, tolerability, and pharmacokinetics of SPL84 single ascending doses (SAD) in healthy volunteers (HV)


Eligibility criteria: Key Inclusion Criteria:

* Male adults 18 to 50 years old
* Considered healthy based on medical history, physical examination, 12-lead ECG and clinical laboratory results
* Body Mass Index (BMI) 19.0-30.0 kg/m2
* Subjects who have no difficulties in receiving drugs by inhalation

Key Exclusion Criteria:

* A major surgical procedure or significant traumatic injury within 28 days prior to study intervention administration
* Recent diagnosis of lung disease (\< 12 weeks from planned enrollment)
* Any acute illness (e.g. acute infection) within 48 hours prior to the study intervention administration, which is considered of clinical significance by the Investigator.
* Chronic respiratory disease including but not limited to obstructive airway disease such as asthma or chronic obstructive pulmonary disease (COPD); restrictive disease such as idiopathic pulmonary fibrosis (IPF); or pulmonary vascular disease such as pulmonary arterial hypertension (PAH).
* History of adverse reactions during aerosol delivery of any medicinal product.
* Total body weight ≤50 kg at screening.
* Abnormal forced expiratory volume at one second (FEV1) at screening.
* Oxygen saturation ≤95% at screening.
* Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and bilirubin (total and direct) above upper limit of normal (ULN) at screening and clinically significant
* Supine systolic blood pressure \<90 or \>140 mmHg, supine diastolic blood pressure \<50 or \>90 mmHg, heart rate \<45 or \>100 beats per minute (bpm), or elevated body temperature (\>38ºC) at screening
* Clinically significant ECG abnormalities at screening
* Positive for SARS-CoV-19 at screening or Day -1 (baseline).
* Positive serology tests for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody at screening.
* Positive urine drug, tobacco, and breath alcohol test result at screening or Day -1 (baseline).
* Use of any prescription or over-the-counter (OTC) medications, including vitamins and herbal or dietary supplements within 14 days prior to dosing.
* Subjects who have received any vaccines within 4 weeks prior to study intervention administration.
* History or current drug/alcohol abuse (excluding use of medicinal cannabis for pain management).
* History of smoking or vaping within 180 days (6 months) of screening

Primary outcomes:
measure: Safety and Tolerability of SPL84 as evaluated by number of subjects with at least one treatment-related adverse event (AE) or serious adverse event (SAEs)
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal systolic and diastolic blood pressure
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal hematology lab test results
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal biochemistry lab test results
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal urinalysis lab test results
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal electrocardiogram (ECG) parameters
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal physical examination findings
timeFrame: Day 1 through Day 31
measure: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal Pulmonary function tests results
timeFrame: Day 1 through Day 31
Secondary outcomes:
measure: Characterization of PK of SPL84: maximum serum concentration (Cmax)
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
measure: Characterization of PK of SPL84: Time to Cmax (Tmax)
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
measure: Characterization of PK of SPL84: terminal elimination half-life (t1/2)
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
measure: Characterization of PK of SPL84: Area under the curve to the final sample (AUC0-t)
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
measure: Characterization of PK of SPL84: Area under the curve to infinity (AUC0-∞)
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
measure: Characterization of PK of SPL84: Apparent clearance (CL/F)
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Hospital Clinical Research Center
Study officials:
References: