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Trial registered on ANZCTR


Registration number
ACTRN12619000962134
Ethics application status
Approved
Date submitted
24/05/2019
Date registered
8/07/2019
Date last updated
8/07/2019
Date data sharing statement initially provided
8/07/2019
Date results information initially provided
8/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase 1, randomized, open-label, single-center, pilot study to evaluate the food effect and pharmacokinetics of single oral doses of XW10172 and sodium oxybate in healthy adult subjects
Scientific title
A phase 1, randomized, open-label, single-center, pilot study to evaluate the food effect and pharmacokinetics of single oral doses of XW10172 and sodium oxybate in healthy adult subjects
Secondary ID [1] 298324 0
XW10172-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Narcolepsy 312961 0
Condition category
Condition code
Neurological 311467 311467 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dose administered: 7.25g of XW10172 or 4.5g of Xyrem per day

Mode of administration: oral solution for both treatments

Duration of administration: 4 days with a 1-day washout in between treatments

Subjects were dosed in one of four following sequences: ABCD, BCDA, CDAB, DABC where A is XW10172 on a 10-hour fast, B is XW10172 after a standard breakfast, C is Xyrem on a 10-hour fast, and D is Xyrem after a standard breakfast


Intervention code [1] 314559 0
Treatment: Drugs
Comparator / control treatment
Comparator: 4.5g of Xyrem oral solution in treatment C and treatment D.

Subjects were dosed in one of 4 following sequences: ABCD, BCDA, CDAB, DABC where A is XW10172 on a 10-hour fast, B is XW10172 after a standard breakfast, C is Xyrem on a 10-hour fast, and D is Xyrem after a standard breakfast


Control group
Active

Outcomes
Primary outcome [1] 320174 0
Pharmacokinetics
To evaluate the pharmacokinetics of using an LC-MS/MS bioanalytical method for analysis of XW10172 and its metabolite oxybate in plasma 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 doses of XW10172 and Xyrem in healthy adult subjects.
Timepoint [1] 320174 0
Pre-dose, and at 0.125, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours post-dose
Secondary outcome [1] 370770 0
Safety
To evaluate the safety 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 Xyrem in healthy adult subjects.
Timepoint [1] 370770 0
Serious Adverse Events with be monitored 30 days post-treatment completion.

Adverse Events will be monitored throughout the duration of the in-house treatment period and at the follow up visit 5 days after check out.

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, respiratory rate, and temperature (in supine 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 each dosing day; approximately the same time as the dosing day 1 to 2 hours assessment on non-dosing days; and at the follow-up visit.

Clinical chemistry, hematology, and urinalysis. Laboratory test samples will be collected at Screening, Check-in, 24 and 36 hours post-dose, and at the follow-up visit.

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
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria

* 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.
* Subjects with pulse oximetry oxygen saturation levels <95% at Screening.
* 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.
* Subject is unwilling to abstain from any strenuous physical exercise (such as weight training, aerobics) 48 hours before the screening examination and 48 hours prior to study admission until the end of the study. Subject may exercise after the screening examination until 48 hours prior to study admission.
* 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)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
ABCD, BCDA, CDAB, DABC where A is XW10172 on a 10-hour fast, B is XW10172 after a standard breakfast, C is Xyrem on a 10-hour fast, and D is Xyrem after a standard breakfast

Simple randomization was used to generate a randomization table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
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
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
Recruitment hospital [1] 13819 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 26576 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 302863 0
Commercial sector/Industry
Name [1] 302863 0
XW Laboratories (Australia) Pty Ltd
Address [1] 302863 0
58 Gipps St
Collingwood VIC 3066
Country [1] 302863 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
XW Laboratories (Australia) Pty Ltd
Address
58 Gipps St
Collingwood VIC 3066
Country
Australia
Secondary sponsor category [1] 302816 0
None
Name [1] 302816 0
Address [1] 302816 0
Country [1] 302816 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303439 0
Bellberry Limited
Ethics committee address [1] 303439 0
129 Glen Osmond Road
Eastwood South Australia 5063
Ethics committee country [1] 303439 0
Australia
Date submitted for ethics approval [1] 303439 0
29/11/2018
Approval date [1] 303439 0
30/11/2018
Ethics approval number [1] 303439 0

Summary
Brief summary
This study is being conducted to evaluate the pharmacokinetics of single oral doses of XW10172 and Xyrem in healthy volunteers under fast and fed conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93670 0
Prof Sepehr Shakib
Address 93670 0

CMAX Clinical Research Pty Ltd
Level 5, 18a North Terrace, Adelaide, SA 5000
Country 93670 0
Australia
Phone 93670 0
+61870887900
Fax 93670 0
Email 93670 0
Sepehr.shakib@adelaide.edu.au
Contact person for public queries
Name 93671 0
Mr William Xiang
Address 93671 0
XW Laboratories Inc.
19F-1, No. 99, Sec. 1, Xintai 5th Rd.
Xizhi Dist., New Taipei City, 221
Country 93671 0
Taiwan, Province Of China
Phone 93671 0
+886966647577
Fax 93671 0
Email 93671 0
william.xiang@xwlabs.com
Contact person for scientific queries
Name 93672 0
Mr William Xiang
Address 93672 0
XW Laboratories Inc.
19F-1, No. 99, Sec. 1, Xintai 5th Rd.
Xizhi Dist., New Taipei City, 221
Country 93672 0
Taiwan, Province Of China
Phone 93672 0
+886966647577
Fax 93672 0
Email 93672 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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary