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Trial registered on ANZCTR


Registration number
ACTRN12615001349538
Ethics application status
Approved
Date submitted
9/12/2015
Date registered
14/12/2015
Date last updated
31/07/2019
Date data sharing statement initially provided
31/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, Open-Label, Single Ascending Dose (SAD) Study of SM04646 Inhalation Solution in Healthy Subjects
Scientific title
A Phase 1, Open-Label Study, to Evaluate the Safety and Tolerability of a Single Inhalation of SM04646 Solution in Healthy Subjects
Secondary ID [1] 287901 0
Nil
Universal Trial Number (UTN)
U1111-1176-5861
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic pulmonary fibrosis (IPF) 296777 0
Condition category
Condition code
Respiratory 297012 297012 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.


Intervention code [1] 293256 0
Treatment: Drugs
Comparator / control treatment
One control subject. The fifth subject enrolled will be administered placebo (vehicle only) nebulisation treatment..
Control group
Placebo

Outcomes
Primary outcome [1] 296607 0
Safety will be evaluated based on the incidence, severity, and seriousness of treatment-emergent AEs, and by changes in clinical laboratory parameters (chemistry, hematology, coagulation indices, and urinalysis), vital signs, O2 saturation levels, electrocardiograms (ECGs), and spirometry results relative to baseline.
Timepoint [1] 296607 0
Treatment emergent adverse events (AE): Every day from Day 1 post study drug administration to end of study Day 90.

Clinical chemistry and haematology parameters and urinalysis from non-fasting blood samples taken on:
Screening Day
Day 1 prior to study drug administration
Days 2, 8, 30 and 90 or early termination post study drug administration

ECG (12 lead) measures taken on:
Screening Day
Day 1 prior to study drug administration, immediate end treatment, 15 minutes, 1, 4 and 8 hours after study drug administration
Days 2, 8, 30 and 90 or early termination post study drug administration

Vital signs measure taken on:
Screening Day
Day 1 prior to study drug administration and at 1, 4 and 8 hours after study drug administration
Days 2, 8, 30 and 90 or early termination post study drug administration

Oxygen Saturation determined from pulse oximeter on:
Day 1 continuously from prior to study drug treatment to 4 hours post study drug administration
Day 1 intermittent 8 and 24 hours post study drug administration
Days 2, 8, 30 and 90 or early termination post study drug administration

Pulmonary Function determined using spirometer test on:
Screening Day
Day 1 prior to study drug administration, immediate end treatment, 15, 30 minutes, 1, 4 and 8 hours after study drug administration
Days 2, 8, 30 and 90 or early termination post study drug administration
Primary outcome [2] 296610 0
To estimate the maximum tolerated dose (MTD) of an inhalation of nebulised SM04646 solution in healthy subjects.
Timepoint [2] 296610 0
7 days of observation of subjects after study drug administration at a cohort dose level and data from these subjects has been reviewed by SRC,

The MTD is considered exceeded for a given dose-level cohort if two or more subjects within that cohort experience a dose limiting toxicicty (DLT) that is determined to be at least possibly related to the active study treatment. If this occurs, the MTD is defined as the previous tolerated dose level administered or an intermediate dose level between the MTD and the previous tolerated dose level, should one be investigated.

If MTD is not exceeded in a dose level cohort 4 new subjects may be treated at the next higher dose level.

If all cohorts are enrolled without exceeding the MTD, the maximum recommended dose (MRD) will be the highest cohort enrolled.
Secondary outcome [1] 318923 0
To characterise the pharmacokinetics of an inhalation of nebulised SM04646 solution in healthy subjects, estimated using available concentration-time data for Cmax, Tmax, AUC0-24hr, AUC0-8, and t1/2 from collected blood samples.
Timepoint [1] 318923 0
Day 1, all within a window of +/- 15 minutes at:
0 minutes (pre-nebulisation)
immediate end of nebulisation
15 minutes, 30 minutes, 1, 2, 4, and 8 hours post-nebulisation

Day 2, within a window of +/- 30 minutes at:
24 hours after Day 1 nebulisation

Day 8 within a window +/- 1 day

Day 30 within a window +/- 2 days

Eligibility
Key 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
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
1) Subjects who are eligible following screening criteria will be enrolled sequentially into escalating dose cohorts of 4 to 5 subjects, with each cohort only enrolling subjects following safety review of the previous dose level by the SRC.

2) The study will include an inhalation tolerability assessment to be performed at the Screening Visit. Potential subjects will be given a placebo (vehicle) nebuliser treatment for 10 minutes to assess tolerability of the inhalation procedure and the vehicle. Subjects will not be enrolled if, in the opinion of the investigator, they are unable to tolerate and complete nebulisation for 10 minutes without significant coughing and/or will not be able to properly partake in study medication administration (inclusion criterion 5).

3) Dose limiting toxicity for this study is defined as the following occurring within 7 days of study drug administration and at least possibly related to the study drug:
- Significant coughs during nebulisation or within 10 minutes following nebulisation. Significant cough would be characterized as causing more discomfort than a mild, easily tolerated AE, and interrupts the subject’s usual daily activities or disrupts ability to deliver the test article by nebulisation.
- A Grade 2 or higher adverse event (AE) per the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
- Specific events concerning respiratory, cardiac, and oxygen saturation levels defined as Moderate or higher
- Emesis, regardless of Grade, within 24 hours of nebulisation
- A serious adverse event (SAE)

Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size for this study was not based on statistical power calculations but is consistent with typical sample sizes used for similar studies to assess preliminary safety.

The general analytical approach for all endpoints will be descriptive in nature, providing a summary and estimate of the safety profile of SM04646 Inhalation Solution in healthy subjects. No formal statistical hypothesis testing will be conducted in this study. All summaries will present the data by dose group as well as by all subjects combined.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
10/11/2015
Date of last participant enrolment
Anticipated
31/01/2016
Actual
13/04/2016
Date of last data collection
Anticipated
Actual
11/07/2016
Sample size
Target
25
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 12220 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 292387 0
Commercial sector/Industry
Name [1] 292387 0
Samumed Pacific Pty Ltd
Country [1] 292387 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Samumed Pacific Pty Ltd
Address
Level 15 Exchange Tower
2 The Esplanade
Perth, WA, 6000
Country
Australia
Secondary sponsor category [1] 291074 0
None
Name [1] 291074 0
Address [1] 291074 0
Country [1] 291074 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293864 0
QIMR Berghofer Medical Research Institute HREC
Ethics committee address [1] 293864 0
Ethics committee country [1] 293864 0
Australia
Date submitted for ethics approval [1] 293864 0
05/05/2015
Approval date [1] 293864 0
04/09/2015
Ethics approval number [1] 293864 0
P2113

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61550 0
Dr Janet WONG
Address 61550 0
Q-Pharm
Level 5 Clive Berghofer Cancer Research Centre
300C Herston Road
Herston Queensland 4006
Country 61550 0
Australia
Phone 61550 0
+61738453647
Fax 61550 0
Email 61550 0
[email protected]
Contact person for public queries
Name 61551 0
Yusuf YAZICI
Address 61551 0
Samumed, LLC
9381 Judicial Dr, Suite 160
San Diego, CA 92121
Country 61551 0
United States of America
Phone 61551 0
+1 858 926 2926
Fax 61551 0
+1 858 926 9315
Email 61551 0
[email protected]
Contact person for scientific queries
Name 61552 0
Yusuf YAZICI
Address 61552 0
Samumed, LLC
9381 Judicial Dr, Suite 160
San Diego, CA 92121
Country 61552 0
United States of America
Phone 61552 0
+1 858 926 2926
Fax 61552 0
+1 858 926 9315
Email 61552 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This trial studies a regulated drug product that was not approved, licensed or cleared by any regulator for any use before the Primary Completion Date of the trial, and the sponsor intends to continue with product development and may at a future date seek regulatory approval, licensure, or clearance of the drug product under study.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.