None listed
Conditions
Brief summary
The purpose of this research study is to learn more about the safety and tolerability of a new experimental drug, SM04646 This is the first time that SM04646 will be administered to humans. Samumed Pacific is developing this small molecule inhibitor (SM04646) of the Wnt pathway to be used for the treatment of Idiopathic Pulmonary Fibrosis (IPF). The pathway is a network of switches in the body that helps to determine what cells become. For this study, a solution containing SM04646 will be nebulised, or made into a fine mist, for inhalation in up to 25 healthy subjects. This study will try to find out the maximum dose of SM04646 that can be safely inhaled by healthy subjects without causing a strong cough response. The purpose of this study is to learn more about the safety and activity of SM04646. to obtain information on how the body absorbs, distributes and removes the drug from the body (pharmacokinetics), blood samples will be taken to measure the concentration of the study drug over time in the body. This study will check safety by measuring heart, lungs, liver and kidney function, number of blood cells and vital signs. Subjects will be treated with a single inhalation of study drug SM04646, on Day 1 be observed for safety for a total of 90 days. The first subject will be administered SM04646 and observed for a minimum of 7 days. The safety of the first subject dosed will be assessed before further subjects are dosed. Subjects will be enrolled into 4 dose groups, with 4 - 5 subjects in each group. Each group will receive a single inhalation of nebulised SM04646 inhalation solution (10 minutes) at doses ranging from 0.7 mg to 20.0 mg. . Eligible subjects will be dosed in a staggered fashion such that no more than two subjects will receive study drug on the same day.
Interventions
A first in human, dose-escalation study in healthy subjects, using a single-dose inhalation of nebulised SM04646. The study drug is in vehicle containing 0.9% mannitol / 0.002% tyloxapol.
Multiple dosing cohorts of 4 -5 subjects will be evaluated until a maximum recommended dose is estimated or the maximum feasible dose (MFD) of 20 mg is reached. Eligible subjects will receive a single inhalation of nebulised SM04646 inhalation solution for 10 minutes on Day 1 and observed for a total of 90 da
A first in human, dose-escalation study in healthy subjects, using a single-dose inhalation of nebulised SM04646. The study drug is in vehicle containing 0.9% mannitol / 0.002% tyloxapol. Multiple dosing cohorts of 4 -5 subjects will be evaluated until a maximum recommended dose is estimated or the maximum feasible dose (MFD) of 20 mg is reached. Eligible subjects will receive a single inhalation of nebulised SM04646 inhalation solution for 10 minutes on Day 1 and observed for a total of 90 days. The dose of SM04646 will be escalated at the following dose levels: 0.7 mg, 2.0 mg, 7.0 mg and 20.0 mg. Eligible subjects will be dosed in a staggered fashion such that no more than two subjects will receive study medication on the same day. The first subject enrolled in study (cohort 1) will be observed for 7 days after study drug administration and data from this subject will be reviewed by a Safety Review Committee (SRC) before remaining Cohort 1 subjects are enrolled. If the first subject experiences a serious adverse event no further subjects will be enrolled.The fifth subject enrolled into cohort 1 will receive the placebo, or vehicle, nebulisation treatment. The SRC will meet following completion of Day 8 assessments for subjects enrolled in each individual cohort to review accumulating safety and tolerability data at each dose level before proceeding to the next dose level of the dose escalation. The SRC will also meet to review all dose limiting toxicities that occur throughout the study to determine if further enrolment may continue for a given cohort or if all further enrolment is to cease. Compliance to the study protocol, applicable regulatory requirements and investigator's obligations will be monitored by Datapharm Australia Pty Ltd on behalf of the sponsor according to ICH GCP guidelines and standard operation procedures. All electronic clinical record forms will by 100% source verified against corresponding source documentation for each subject and includes but not limited to drug accountability and preparation procedures, appropriate consenting procedures and adherence to dosing procedures.. At site monitoring will be carried out according to the schedule outlined in the monitoring plan.and includes for cause visits if need arises.
Sponsors
Samumed Pacific Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
In good general health; Able to comprehend and willing to sign an informed consent form; Able to tolerate and complete placebo (vehicle) inhalation for 10 minutes without experiencing a significant cough
Exclusion criteria
Women who are pregnant or lactating; Women of childbearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period; Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized, that are not using a highly effective method of birth control during the study treatment period until 90 days post study medication administration; Males unwilling to refrain from sperm donation during the study treatment period until 90 days post study medication administration; Current smoker, or past history of smoking within 6 months or >10 pack years Receipt of any of the following medication or treatment prior to the Screening Visit: a. Prescription medication within 7 days prior to the Screening Visit, except for prescription birth control b. Previous therapeutic radiation treatment of the lungs, mediastinum, or chest wall c. Current use of NSAIDs or aspirin (within 24 hours of the Screening Visit) d. Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure within 1 month or 5 half-lives of the investigational product, whichever is longer, prior to the Screening Visit; History of any of the following conditions: a. Idiopathic pulmonary fibrosis b. Pulmonary embolism or pulmonary hypertension c. Congenital respiratory conditions (e.g. cystic fibrosis) d. Chronic obstructive pulmonary disease (COPD) e. HIV, hepatitis C, or active hepatitis B infection f. Hepatic cirrhosis g. Lower respiratory tract infection within 30 days prior to the Screening Visit h. Coronary artery disease, congestive heart failure, or myocardial infarction i. Restrictive or obstructive lung disease j. Hypertension k. Hypotension l. Any condition that is dependent on oxygen therapy; Clinically significant abnormal hematology values or blood chemistry values; History of clinically significant cardiac arrhythmia
Outcome results
None listed