COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04296799




Registration number
NCT04296799
Ethics application status
Date submitted
26/02/2020
Date registered
5/03/2020
Date last updated
23/07/2020

Titles & IDs
Public title
A Phase 1 Study of SMP-100 in Normal Healthy Volunteers
Scientific title
Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SMP-100 in Normal Healthy Volunteers
Secondary ID [1] 0 0
ChengduSciMount
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SMP-100
Treatment: Drugs - Placebo

Experimental: Single Ascending Dose - The study will consist of 6 cohorts (1 cohort per dose level) of 8 subjects (6 subjects receiving the study drug and 2 receiving matching placebo), for a total of 48 subjects.

Experimental: Multiple Ascending Dose - The study will consist of 3 cohorts (1 cohort per dose level) of 8 subjects. Six subjects will receive study drug and 2 subjects will receive matching placebo, daily for 14 consecutive days, for a total of 24 subjects (18 study drug; 6 placebo).


Treatment: Drugs: SMP-100
SAD/MAD

Treatment: Drugs: Placebo
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Endpoints of SAD - Number of subjects with adverse events (AEs) (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead electrocardiogram (ECGs), clinical laboratory parameters, weight, and physical examination.
Timepoint [1] 0 0
10±2 days post dose
Primary outcome [2] 0 0
Safety Endpoints of MAD - Number of subjects with adverse events (AEs) (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead electrocardiogram (ECGs), clinical laboratory parameters, weight, and physical examination.
Timepoint [2] 0 0
13±2 days post last dose
Secondary outcome [1] 0 0
PK Endpoints AUC0-t of SAD - area under the concentration-time curve from time zero to the last non-zero concentration (AUC0-t)
Timepoint [1] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [2] 0 0
PK Endpoints AUC0-24 of SAD - area under the concentration-time curve from time zero to time 24 hours (AUC0-24)
Timepoint [2] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [3] 0 0
PK Endpoints AUC0 inf of SAD - area under the concentration-time curve from time zero to infinity (extrapolated) (AUC0 inf)
Timepoint [3] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [4] 0 0
PK Endpoints Cmax of SAD - maximum plasma concentration (Cmax)
Timepoint [4] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [5] 0 0
PK Endpoints Tmax of SAD - time of maximum concentration ( Tmax)
Timepoint [5] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [6] 0 0
PK Endpoints T½ el of SAD - elimination half-life ( T½ el)
Timepoint [6] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [7] 0 0
PK Endpoints Cl/F of SAD - Total body clearance, calculated as Dose / AUC0-inf (Cl/F)
Timepoint [7] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [8] 0 0
PK Endpoints Vz/F of SAD - apparent volume of distribution, calculated as Dose / (Kel * AUC0-inf) (Vz/F)
Timepoint [8] 0 0
before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours post-dose.
Secondary outcome [9] 0 0
PK Endpoints AUC0-24 of MAD - area under the concentration-time curve from time zero to time 24 hours (AUC0-24)
Timepoint [9] 0 0
Day 1
Secondary outcome [10] 0 0
PK Endpoints Cmax of MAD - maximum plasma concentration (Cmax)
Timepoint [10] 0 0
Day 1
Secondary outcome [11] 0 0
PK Endpoints Tmax of MAD - time of maximum concentration ( Tmax)
Timepoint [11] 0 0
Day 1
Secondary outcome [12] 0 0
PK Endpoints T½ el of MAD - elimination half-life ( T½ el)
Timepoint [12] 0 0
Day 1
Secondary outcome [13] 0 0
PK Endpoints AUC0-t of MAD - area under the concentration-time curve at steady-state from time zero to time 24 hours ( AUC0-t)
Timepoint [13] 0 0
Day 14
Secondary outcome [14] 0 0
PK Endpoints AUC0-48 of MAD - area under the concentration-time curve from time zero to time 48 hours ( AUC0-48)
Timepoint [14] 0 0
Day 14
Secondary outcome [15] 0 0
PK Endpoints AUC0-72 of MAD - area under the concentration-time curve from time zero to time 72 hours ( AUC0-72)
Timepoint [15] 0 0
Day 14
Secondary outcome [16] 0 0
PK Endpoints Cmax ss of MAD - maximum observed concentration at steady-state (Cmax ss)
Timepoint [16] 0 0
Day 14
Secondary outcome [17] 0 0
PK Endpoints Tmax ss of MAD - time of maximum concentration at steady-state(Tmax ss)
Timepoint [17] 0 0
Day 14
Secondary outcome [18] 0 0
PK Endpoints Cmin ss of MAD - minimum observed concentration at steady-state(Cmin ss)
Timepoint [18] 0 0
Day 14
Secondary outcome [19] 0 0
PK Endpoints AUC0- t of MAD - area under the concentration-time curve from time zero to the last non-zero concentration(AUC0- t)
Timepoint [19] 0 0
Day 14
Secondary outcome [20] 0 0
PK Endpoints T½ el of MAD - elimination half-life(T½ el)
Timepoint [20] 0 0
Day 14
Secondary outcome [21] 0 0
PK Endpoints Clss/F of MAD - total body clearance at steady-state, calculated as Dose / AUC0-inf(Clss/F)
Timepoint [21] 0 0
Day 14
Secondary outcome [22] 0 0
PK Endpoints Vz ss/F of MAD - apparent volume of distribution at steady-state, calculated as Dose / (Kel * AUC0-inf)(Vz ss/F)
Timepoint [22] 0 0
Day 14
Secondary outcome [23] 0 0
Plasma concentration observed of MAD - Plasma concentration observed will be presented
Timepoint [23] 0 0
before treatment administrations (Ctrough) during repeated dosing (Days 2-13)

Eligibility
Key inclusion criteria
1. Male or female, non-smoker (no use of tobacco or nicotine products within 3 months
prior to screening) aged between =18 and =59 years old.

2. BMI >18.5 and <30.0 kg/m2 and body weight =50.0 kg for males and =45.0 kg for females.

3. Healthy as defined by:

1. the absence of clinically significant illness and surgery within 4 weeks prior to
dosing.

2. the absence of clinically significant history of neurological, endocrine,
cardiovascular, respiratory, hematological, immunological, psychiatric,
gastrointestinal, renal, hepatic, and metabolic disease.

3. the absence of clinically significant history of constipation, diarrhea, or
irregular bowel transit in the last 4 weeks.

4. the absence of clinically significant history of irritable bowel syndrome (IBS)
of any type.

5. the absence of current or history of ischemic colitis.

4. Females of childbearing potential who are sexually active with a non-sterile male
partner (sterile male partners are defined as men vasectomized since at least 6
months) must be willing to use one of the following acceptable contraceptive methods
throughout the study and for 30 days after (the last) study drug administration:

1. simultaneous use of intra-uterine contraceptive device placed at least 4 weeks
prior to (the first) study drug administration, and condom for the male partner;

2. simultaneous use of hormonal contraceptive starting at least 4 weeks prior to
(the first) study drug administration and must agree to use the same hormonal
contraceptive throughout the study, and condom for the male partner;

3. simultaneous use of diaphragm or cervical cap and male condom for the male
partner, started at least 21 days prior to (the first) study drug administration.

A woman is considered of childbearing potential unless she is surgically sterilized
(hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks
before screening or postmenopausal (where postmenopausal is defined as no menses for
12 months without an alternative medical cause).

5. Male subjects who are not vasectomized for at least 6 months, and who are sexually
active with a female partner of childbearing potential (childbearing potential females
are defined as women that are neither post-menopausal nor surgically sterile) must be
willing to use one of the following acceptable contraceptive methods from the first
study drug administration until at least 90 days after the last study drug
administration:

1. simultaneous use of a male condom and, for the female partner, hormonal
contraceptives used since at least 4 weeks or intra-uterine contraceptive device
placed since at least 4 weeks;

2. simultaneous use of a male condom and, for the female partner, a diaphragm.

6. Male subjects (including men who have had a vasectomy) with a pregnant or same-sex
partner must agree to use a condom from the first study drug administration until at
least 90 days after the last study drug administration.

7. Male subjects must be willing not to donate sperm until 90 days following the last
study drug administration.

8. Willing to take off dentures or mouth piercing at the time of dosing.

9. Capable of consent.
Minimum age
18 Years
Maximum age
59 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any clinically significant abnormality at physical examination.

2. Any clinically significant abnormal laboratory test results or positive test for
hepatitis B, hepatitis C, or HIV found during medical screening.

3. Positive urine drug screen, alcohol breath test, or urine cotinine test at screening.
A repeat test can be conducted at screening or Day -1 at the discretion of the
Principal Investigator or delegate.

4. History of allergic reactions to SMP-100 or other related drugs, or to any excipient
in the formulation.

5. History of hypersensitivity to 5-HT3 receptor antagonists or agonists.

6. Positive serum pregnancy test at screening.

7. Clinically significant ECG abnormalities (QTcF >450 ms for males and QTcF >460 ms for
females).

8. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90
or over 159 mmHg, diastolic blood pressure lower than 50 or over 100 mmHg, or heart
rate less than 50 or over 100 bpm) at screening. Repeat test can be conducted at
screening or Day -1 at the discretion of the Principal Investigator or delegate.

9. Clinically significant orthostatic vital sign abnormalities such as decrease in
systolic blood pressure of 20 mmHg or higher, decrease in diastolic blood pressure of
10 mmHg or higher, or increase in heart rate of 30 bpm or higher within 3 minutes
after passing from a supine to a standing position. Repeat test can be conducted at
screening or Day -1 at the discretion of the principal investigator or delegate.

10. History of significant alcohol abuse within 1 year prior to screening or regular use
of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol
per week [1 unit = 150 mL of wine, 375 mL of mid strength beer, or 30 mL of 40%
alcohol]).

11. History of significant drug abuse within 1 year prior to screening or use of drugs
such as marijuana within 3 months prior to the screening visit or drugs such as
cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and
amphetamine derivatives within 1 year prior to screening.

12. Participation in a clinical research study involving the administration of an
investigational drug or device within 30 days prior to the first dosing.

13. Administration of a biological product in the context of a clinical research study
within 90 days prior to the first dosing.

14. Use of medications for the timeframes specified below, with the exception of
medications exempted by the Investigator on a case-by-case basis because they are
judged unlikely to affect the PK profile of the study drug or subject safety (e.g.,
topical drug products without significant systemic absorption):

1. prescription medications within 14 days prior to the first dosing;

2. over-the-counter products and natural health products (including herbal remedies
homeopathic and traditional medicines, probiotics, food supplements such as
vitamins, minerals, amino acids, essential fatty acids, and protein supplements
used in sports) within 14 days prior to the first dosing, with the exception of
the occasional use of paracetamol (up to 2 g daily);

3. any prescription or over-the-counter medication or natural health products used
for the treatment of irregular bowel transit (e.g. diarrhea, constipation) within
4 weeks prior to the first dosing;

4. depot injection or implant of any drug within 3 months prior to the first dosing;

5. use of any drugs known to induce or inhibit hepatic metabolism (including St.
John's Wort [hypericin]) within 14 days prior to the first dosing.

15. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding
volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than
499 mL within 56 days prior to the first dosing.

16. Presence of:

1. orthodontic braces or orthodontic retention wires, or

2. any physical findings in the mouth or tongue that would be likely to interfere
with successful completion of the dosing procedure.

17. Breast-feeding subject.

18. Any reason which, in the opinion of the Investigator, would prevent the subject from
participating in 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
Recruitment hospital [1] 0 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
SA 5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Chengdu SciMount Pharmatech Co., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This will be the first clinical study of oral administration SMP-100 in healthy subjects. The
proposed randomized Phase 1 trial is a double-blind, placebo-controlled, single and multiple
ascending dose study in approximately 72 healthy male and female subjects.
Trial website
https://clinicaltrials.gov/show/NCT04296799
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Polasek
Address 0 0
CMAX Clinical Research Pty Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dejian Xie
Address 0 0
Country 0 0
Phone 0 0
+8617761298792
Fax 0 0
Email 0 0
dejianx@xilinglab.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04296799