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Trial registered on ANZCTR


Registration number
ACTRN12618000127202
Ethics application status
Approved
Date submitted
9/01/2018
Date registered
30/01/2018
Date last updated
27/05/2019
Date data sharing statement initially provided
27/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of ascending single oral doses of XW10172 in healthy adult subjects
Scientific title
A phase 1, randomized, double-blind, single-center, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics of ascending single oral doses of XW10172 in healthy adult subjects
Secondary ID [1] 293668 0
XW10172-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Narcolepsy 305957 0
Condition category
Condition code
Inflammatory and Immune System 305156 305156 0 0
Autoimmune diseases
Neurological 305157 305157 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ascending single dose of XW10172 as an oral solution. Proposed dose escalation schedule (grams): 0.1, 0.5, 1.5, 3, 4.5, 6, 7.25.

Monitor adherence to the intervention will be through direct observation and a purified water rinsing of the amber glass bottle to ensure the entire experimental treatment is consumed.
Intervention code [1] 299927 0
Treatment: Drugs
Comparator / control treatment
Placebo oral solution.

The excipients used in the placebo oral solution are purified water, malic acid, sucralose and essence (strawberry).
Control group
Placebo

Outcomes
Primary outcome [1] 304364 0
Safety and Tolerability
To evaluate the safety and tolerability endpoints including adverse events monitoring (incidence, severity and causality), clinical laboratory abnormalities (incidence and severity), changes from baseline in vital signs (blood pressure, temperature, respiratory rate, heart rate and pulse oximetry), clinical findings on physical examination (incidence and severity) and changes from baseline in 12-lead ECG parameters of single ascending doses of XW10172 and placebo in healthy adult subjects.
Timepoint [1] 304364 0
Serious Adverse Events with be monitored 30 days post-treatment.

Adverse Events will be monitored throughout the duration of the in-house treatment period and follow up for a total period of 5 days.

Twelve-lead ECGs will be performed in triplicate with each individual ECG in the triplicate obtained at least 1 minute apart. Subjects should be resting in the supine position for at least 10 minutes prior to each ECG. Electrocardiograms will be taken at Screening; pre-dose; 0.5, 1, 2, 4, 8, 24, and 36 hours post-dose; and at the follow-up visit.

Vital signs include blood pressure, heart rate, temperature, and respiratory rate (in sitting position after a 10-minute rest). Measurements will be taken at screening; Day -1; pre-dose, 1 to 2 hours, 4 to 6 hours post-dose on Day 1; approximately the same time as the Day 1 1 to 2 hours assessment on Days 2 and 3; and at the follow-up visit.

Clinical chemistry, hematology, and urinalysis. Blood samples will be collected at Screening, Day -1, 24 and 36 hours post-dose, and at the follow-up visit.
Secondary outcome [1] 341740 0
Pharmacokinetics
To evaluate the pharmacokinetics of using an LC-MS/MS bioanalytical method for analysis of XW10172 and its metabolite oxybate including maximum concentration (Cmax) and trough concentration (Cmin), Time to reach Cmax (Tmax), Area under the concentration-time curve (AUC), apparent terminal half-life (T1/2), Cmax and AUC ratios of oxybate to XW10172 and apparent oral clearance (CL/F) of single ascending doses of XW10172 in healthy adult subjects.
Timepoint [1] 341740 0
0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.

Eligibility
Key inclusion criteria
*Healthy male and female subjects age 18 to 45 years of age (inclusive). Healthy is defined as no clinically relevant abnormalities as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at Screening.
*Body mass index of 18 to 30 kg/m^2, inclusive, and a total body weight >50 kg (110 lbs).
*Female subjects of nonchildbearing potential, defined as surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or clinically documented to be postmenopausal (no regular menstrual bleeding for at least 1 year prior to study start and follicle-stimulating hormone >40 IU/L).
*Female subjects of childbearing potential must have a confirmed negative pregnancy test at the start of the study (Screening and Check-in) and also agree to abstain from sexual intercourse or use a highly effective method of birth control for the duration of the study, as determined by the investigator. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., <1% per year) when used consistently and correctly, such as condom + diaphragm, or intrauterine device (IUD) with documented failure rate of <1% per year, implanted hormonal contraceptives, or oral/injectable contraceptives used in combination with an additional barrier method.
Male subjects must agree to abstain from sexual intercourse or use a highly effective method of birth control with partners of childbearing potential for the duration of the study and for 1 month after last dose of study drug. A highly effective method of birth control in male subjects includes vasectomy or the use of a condom in combination with barrier methods, hormonal birth control or IUD by the female partner.
*Subjects with creatinine clearance greater than or equal to 60 mL/min and alanine aminotransferase, aspartate aminotransferase levels of less than or equal to 1.0 multiplied by ~ upper limit of normal.
*Signed and dated written informed consent prior to admission to the study in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) and local regulations.
*Subjects who are willing and able to comply with the scheduled visits, laboratory tests, and other study procedures as stated in this protocol.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Subjects with pulse oximetry oxygen saturation levels <95% at Screening.
* Evidence or history of clinically significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, psychiatric, neurological, immunological or hormonal disorders, or allergic disease (including drug allergies, including immediate type hypersensitivity).
* History of major depression, obstructive sleep apnea, epilepsy, and seizures.
* Risk of suicidality at Screening as assessed using Columbia Suicide Assessment Test.
* Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations.
* Donation or loss of 500 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
* Use of tobacco- or nicotine-containing products within 3 months prior to check-in and positive urine cotinine test at Screening or check-in.
* History of drug or alcohol abuse (>14 units per week for males or >7 units per week for females [1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits]) within the 5 years prior to dosing or evidence of such abuse as indicated by a positive urine drug screen and/or positive alcohol screen done at Screening or Check-in.
* Subjects with any condition which may affect drug absorption, distribution, metabolism, or excretion.
* Subject has clinically significant abnormalities on 12-lead ECG based on investigator’s judgment, or any of the following abnormalities at the screening visit or Day 1 predose: PR >200 msec, QRS complex >120 msec, and/or QTCF >450 msec.
* Use of prescription or non-prescription drugs, vitamins and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to first dose of study drug. Subjects who are concurrently using any drug known to affect sleep-wake function.
* Pregnant or breast-feeding women.
* Subjects with known hypersensitivity to any components of the study drug.
* Subjects are unwilling to comply with the protocol requirements, instructions, and study-related restrictions.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Emergency code-break envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Demographic, baseline characteristic, safety, and PK data will be summarized descriptively. Statistical analyses will be performed by using SAS 'Registered Trademark' version 9.3 or higher (SAS Institute, Cary NC, USA).
The standard summary statistics for continuous variables are sample size (n), mean, standard deviation (SD), standard error of the mean (SEM), median, minimum and maximum. The standard summary statistics for categorical variables are frequencies and percentages.
Individual data (including relevant derived variables) will be presented by parameter in listings. Results of statistical analyses, descriptive summary statistics and supportive listings will also be presented.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/02/2018
Actual
13/02/2018
Date of last participant enrolment
Anticipated
28/06/2018
Actual
28/06/2018
Date of last data collection
Anticipated
2/08/2018
Actual
2/07/2018
Sample size
Target
50
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 9637 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 18394 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 298288 0
Commercial sector/Industry
Name [1] 298288 0
XW Laboratories (Australia) Pty Ltd
Country [1] 298288 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
XW Laboratories (Australia) Pty Ltd
Address
58 Gipps St
Collingwood VIC 3066
AU
Country
Australia
Secondary sponsor category [1] 297403 0
None
Name [1] 297403 0
Address [1] 297403 0
Country [1] 297403 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299287 0
Bellberry Limited
Ethics committee address [1] 299287 0
Ethics committee country [1] 299287 0
Australia
Date submitted for ethics approval [1] 299287 0
06/12/2017
Approval date [1] 299287 0
18/01/2018
Ethics approval number [1] 299287 0

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

Contacts
Principal investigator
Name 79918 0
Prof Sepehr Shakib
Address 79918 0
CMAX Clinical Research Pty Ltd
Level 5, 18a North Terrace
Adelaide SA 5000
Country 79918 0
Australia
Phone 79918 0
+61870887900
Fax 79918 0
+61870887999
Email 79918 0
sepehr.shakib@adelaide.edu.au
Contact person for public queries
Name 79919 0
William Xiang
Address 79919 0
XW Laboratories (Australia) Pty Ltd
58 Gipps St
Collingwood VIC 3066
Country 79919 0
Australia
Phone 79919 0
+886966647577
Fax 79919 0
Email 79919 0
william.xiang@xwlabs.com
Contact person for scientific queries
Name 79920 0
William Xiang
Address 79920 0
XW Laboratories (Australia) Pty Ltd
58 Gipps St
Collingwood VIC 3066
Country 79920 0
Australia
Phone 79920 0
+886966647577
Fax 79920 0
Email 79920 0
william.xiang@xwlabs.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ownership of data and future intellectual property filing.


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.