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Trial registered on ANZCTR


Registration number
ACTRN12619000327189
Ethics application status
Approved
Date submitted
11/02/2019
Date registered
4/03/2019
Date last updated
27/05/2019
Date data sharing statement initially provided
4/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of a Single Ascending Dose of SM07883, a Novel DYRK1a Inhibitor, Following Oral Administration to Healthy Subjects
Scientific title
A Phase 1, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of a Single Ascending Dose of SM07883, a Novel DYRK1a Inhibitor, Following Oral Administration to Healthy Subjects
Secondary ID [1] 295930 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 309427 0
Condition category
Condition code
Neurological 308278 308278 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This Phase I study is a first-in-human, single dose, dose escalation safety study in healthy volunteers. Participants will be administered SM07883 orally as a single dose.

Sequential dose cohorts of healthy participants will receive a single fixed dose of SM07883 at 5, 10, 15, 30, 60, 120, or 180 mg followed by a 28-day observation period.

Safety data for each cohort will be reviewed by the Safety Review Committee (SRC) prior to escalation to the next cohort.
Intervention code [1] 312252 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307250 0
Safety and tolerability of oral SM07883 administered as a single-dose and assessed by the following;
- incidence and severity of clinical laboratory abnormalities,
- change from baseline in vital sign measurements (blood pressure, temperature, respiratory rate, pulse rate),
-electrocardiograms (ECGs) and
- incidence, severity, and relationship to study medication of adverse events (AEs) from Day 1.

This is the first time that humans have taken this medication. It is unknown whether the medication is tolerable and safe in healthy subjects, or if the medication will be effective, including the specific dosage (maximum dosage of 180mg, if lower doses are assessed as tolerable and safe), for healthy subjects

As this is the first time that humans have taken this solution, there may be undesirable side effects, including:
- Photosensitivity
- In animals, repeated (28 days) high doses of the study medication, SM07883, caused minimal abnormalities in the testicles and epididymis (the tube at the back of the testicle that stores and carries sperm). No effect on sperm production was seen. Although laboratory and animal studies have been done to review possible risks, The results do not necessarily show what will happen when the medication is taken by humans.

All subjects will be asked to report any adverse events to study personnel at their visits. Study personnel will assess all events for relationship to study medication.
Timepoint [1] 307250 0
Clinical Laboratory test samples taken on:
Screening Visit,
Day 1 (pre drug administration)
Days 2,3,4,7,14,21 and 28 after single-dose administration or early termination

Vital Sign measurements taken on:
Screening Visit
Day -3 (for dosing cohorts of 30 mg or greater)
Day 1 (pre and post drug administration)
Days 2, 3, 4, 7, 14, 21 and 28 days after single-dose administration or early termination.

ECG measurements taken on:
Screening Visit
Day 1 (pre and post drug administration)
Days 2, 3, 4, 7 and 28 days after single-dose administration or early termination

AEs are assessed everyday from commencement through to Day 28 (or through the observation period of ongoing AEs).
Primary outcome [2] 307252 0
Characterise the systemic exposure and pharmacokinetics (PK), as appropriate, of oral SM07883 following a single dose administration to healthy subjects.

SM07883 plasma concentrations will be summarized for the evaluation of systemic exposure and PK parameters will be estimated and summarized when possible (with appropriate plasma concentration-time data). The following PK parameters may be estimated for subjects in the PK Analysis Set:

- Cmax Maximum observed plasma concentration
- tmax Time to Cmax
- AUC0-24 Area under the plasma concentration-time curve from 0 to 24 hours
- AUC0-last Area under the plasma concentration-time curve from 0 to last measurable concentration
- AUC0-inf Area under the plasma concentration-time curve from 0 to infinite time
- t1/2 Apparent plasma terminal phase half-life

Dose proportionality across treatment cohorts will also be assessed.
Timepoint [2] 307252 0
PK blood samples taken on:
Day 1 (pre and post drug administration)
Days 2, 3, 4, and 7 after single-dose administration
Secondary outcome [1] 351271 0
Exposure and tolerability relationship, as appropriate.
Timepoint [1] 351271 0
AEs are assessed everyday from commencement through to Day 28 (or through the observation period of ongoing AEs).
Secondary outcome [2] 351273 0
Concentration of metabolites associated with SM07883 including, but not limited to, SM07882 and SM09859, in plasma.
Timepoint [2] 351273 0
Plasma PK samples taken on:
Day 1 (pre and post drug administration)
Days 2, 3, 4, and 7 after single-dose administration
Secondary outcome [3] 351278 0
Concentration of SM07883 in urine.
Timepoint [3] 351278 0
Urine PK samples taken on:
Day 1 (post drug administration)
Days 2, 3, and 4 after single-dose administration
Secondary outcome [4] 351283 0
Concentration of SM07883 in cerebrospinal fluid (CSF) at all doses 30 mg or greater.
Timepoint [4] 351283 0
CSF samples taken on:
Day -3
Day 1 (post drug administration) at tmax (determined by lower dose cohorts)
Secondary outcome [5] 367618 0
Concentration of metabolites associated with SM07883 including, but not limited to, SM07882, and SM09859, in urine.
Timepoint [5] 367618 0
Urine PK samples taken on:
Day 1 (post drug administration)
Days 2, 3, and 4 after single-dose administration
Secondary outcome [6] 367619 0
Concentration of metabolites associated with SM07883 including, but not limited to, SM07882 and SM09859, in cerebrospinal fluid (CSF) at all doses 30 mg or greater.
Timepoint [6] 367619 0
CSF samples taken on:
Day -3
Day 1 (post drug administration) at tmax (determined by lower dose cohorts)

Eligibility
Key inclusion criteria
1. Healthy adult females 18 to 70 years old; or, healthy adult males 18 to 70 years old, who are surgically sterile; or, healthy adult males greater than 55 years old with no interest in fathering a child in the future
2. Body mass index (BMI) of 19 to 30, inclusive
3. Subject must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed.
4. Willingness and ability to comply with all scheduled study visits, laboratory tests, contraception requirements, and other study procedures.
5. Willing to avoid extensive sun exposure, phototherapy, or use of a tanning salon for the duration of the study.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Women who are pregnant, lactating, or have a positive or indeterminate pregnancy result
2. Women of childbearing potential who are sexually active, and who are not willing to use an acceptable method of birth control during the study period
3. Men up to 55 years old (inclusive) who are of childbearing potential
4. Men greater than 55 years old of childbearing potential who may wish to father a child in the future
5. Men greater than 55 years old of childbearing potential who are sexually active and have a partner who is capable of becoming pregnant, neither of whom are agreeable to using an acceptable method of birth control
6. History of or current allergy to investigational product ingredients.
7. Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, musculoskeletal, immunologic, neurologic, or dermatologic disease
8. History of malignancy within the last 5 years
9. Recent treatment with an investigational product.
10. History of long QT syndrome and/or clinically significant ECG
11. History of clinically significant increased intracranial pressure, bleeding diathesis, cardiopulmonary instability, or soft tissue infection at the proposed puncture site
12. Clinically significant laboratory abnormalities at Screening
13. Recent active infection or febrile illness
14. Recent serious illness requiring hospitalization
15. Any chronic condition that has not been well controlled. 16. Uncontrolled hypertension
17. Regular alcohol abuse
18. A history of abuse of prescription or illicit drugs
19. Positive urine drug screen
20. Recent use of strong inhibitors or inducers of CYP3A4 and CYP2D6 enzymes (eg grapefruit, grapefruit juice, and star fruit).
21. Subjects who have a current or pending disability claim, workers’ compensation, or litigation(s)
22. Subjects who are immediate family members of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site.
23. Subjects employed by Samumed Pacific Pty Ltd, or any of its affiliates or development partners responsible for the conduct of the study

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)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 300528 0
Commercial sector/Industry
Name [1] 300528 0
Samumed Pacific Pty Ltd
Address [1] 300528 0
Level 15 Exchange Tower,
2 The Esplanade,
Perth, Western Australia, 6000,
Australia
Country [1] 300528 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Samumed Pacific Pty Ltd
Address
Level 15 Exchange Tower,
2 The Esplanade,
Perth, Western Australia, 6000,
Australia
Country
Australia
Secondary sponsor category [1] 300003 0
None
Name [1] 300003 0
Address [1] 300003 0
Country [1] 300003 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301316 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 301316 0
Level 3, Roma Mitchell House,
136 North Terrace,
Adelaide, SA 5000
Ethics committee country [1] 301316 0
Australia
Date submitted for ethics approval [1] 301316 0
10/08/2018
Approval date [1] 301316 0
20/12/2018
Ethics approval number [1] 301316 0

Summary
Brief summary
Alzheimer’s disease is the most common cause of dementia in older adults and affects millions of people in Australia and worldwide. Alzheimer’s disease causes loss of memory, difficulty in thought and reasoning, and behavioural changes. There are currently no effective treatments that slow or stop the progression of Alzheimer’s disease. In an effort to address the need for medications that treat Alzheimer’s disease, Samumed, LCC (the sponsor) has developed a new investigational drug, SM07883. SM07883 is a novel small molecule inhibitor of DYRK1a which has been tested in a number of non-clinical studies.

This study is a first-in-human, single dose, dose-escalation safety study in healthy subjects 18-70 years old. Subjects who provide written informed consent for this study will undergo baseline evaluations at the Screening visit. Subjects will participate in a screening period of up to 21 days and a 28-day observation period.

Sequential dose cohorts of healthy subjects will receive a single fixed dose of SM07883 at 5, 10, 15, 30, 60, 120 and 180 mg. Each cohort will consist of 4-6 subjects. Safety data from each cohort will be reviewed by a Safety Review Committee prior to continuing to the next cohort.

The purpose of this study is to learn more about the safety of SM07883, how well it is tolerated, and what happens to it in the body when given as a single dose oral tablet to healthy subjects. The findings from this study will support future studies in Alzheimer’s patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86610 0
Prof Guy LUBROOK
Address 86610 0
PARC Clinical Research
Royal Adelaide Hospital
Port Rd Adelaide SA 5000
Country 86610 0
Australia
Phone 86610 0
+61 413 817 901
Fax 86610 0
Email 86610 0
guy.ludbrook@sa.gov.au
Contact person for public queries
Name 86611 0
Dr Yusuf YAZICI
Address 86611 0
Samumed, LLC
9381 Judicial Dr, Suite 160
San Diego, CA 92121
Country 86611 0
United States of America
Phone 86611 0
+1 858 926 2926
Fax 86611 0
+1 858 926 9315
Email 86611 0
yusuf@samumed.com
Contact person for scientific queries
Name 86612 0
Dr Yusuf YAZICI
Address 86612 0
Samumed, LLC
9381 Judicial Dr, Suite 160
San Diego, CA 92121
Country 86612 0
United States of America
Phone 86612 0
+1 858 926 2926
Fax 86612 0
+1 858 926 9315
Email 86612 0
yusuf@samumed.com

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 will not be 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 other documents available
Summary results
No Results