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Trial registered on ANZCTR


Registration number
ACTRN12618000205235
Ethics application status
Approved
Date submitted
9/01/2018
Date registered
8/02/2018
Date last updated
22/08/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A healthy volunteer study to test the safety and tolerability of a single dose of the Dexmedetomidine Transdermal System as well as how your body takes it in and disposes and breaks it down.
Scientific title
A Safety and Pharmacokinetics Study of Single Dose Dexmedetomidine Transdermal System in Healthy Subjects
Secondary ID [1] 293709 0
None
Universal Trial Number (UTN)
U1111-1207-1717
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Pain Management in postoperative setting 306057 0
Condition category
Condition code
Anaesthesiology 305194 305194 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dexmedetomidine Transdermal System (DMTS) is a 3 cm squared patch with each patch containing 0.73 mg of dexmedetomidine. The patch will be applied by the trained site staff and worn for 4 consecutive days without any patch changes. Each patch will be applied to a non-hairy portion of the subject's upper arm. Each patch will be visually checked for adhesion everyday (6, 12, 24, 28, and 72 hours after patch application and immediately prior to patch removal) by the trained site staff to ensure each patch is still properly adhered to the subject

This study is also looking to identify an appropriate hydration regimen. This will be administered 2 hours before patch application through to 6-12 hours after patch application.

There are 5 cohorts. Cohort 1 - 4 will receive 1 application of 2 patches and cohort 5 will receive 1 application of 1 patch. Subjects will be required to drink a defined amount of liquid based on cohort:
Cohort 1 subjects will be required to drink 4 litres of liquid over a 14-hour period starting 2 hours prior to patch application.
Cohort 2 subjects will be required to drink 4 litres of liquid over an 8-hour period, starting 2 hours prior to patch application.
Cohort 3 subjects will be required to drink 3 litres of liquid over an 8-hour period, starting 2 hours prior to patch application.
Cohort 4 subjects will be required to drink 2 litres of liquid over an 8-hour period, starting 2 hours prior to patch application.
Cohort 5 subjects will receive a hydration regimen determined to be acceptable based on findings from Cohorts 2 - 4. The Safety Monitoring Committee will review the findings and a decision will be made when the Safety Monitoring Committee meets after the completion of Cohort 4.

Each subject will be instructed to drink 1 litre of liquid 2 hours prior to patch application. After patch application, the subjects will be asked to drink the following:
Cohort 1: 1 litre to drink every 4 hours until 3 litres are orally ingested.
Cohort 2: 1 litre every 2 hours to drink until 3 litres are orally ingested.
Cohort 3: 1 litre every 3 hours to drink until 2 litres are orally ingested.
Cohort 4: 0.5 litre every 3 hours until 1 litre is orally ingested.
Cohort 5's liquid consumption schedule will be determined after the safety meeting.

Each subject's liquid consumption will be supervised by the site staff.

Once the patches are removed, there is a 48 hour washout period before the subject can be discharged from the clinic.
Intervention code [1] 299964 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304353 0
To assess the safety of the DMTS following a single 4-day application in healthy volunteers with a BMI in the range of 18.0 to 22.0 receiving a hydration regimen as assess by the collection of safety data, such as adverse events, clinical laboratory tests, vital signs, ECGs, cardiac telemetry, skin irritation assessments, and physical exams.

Timepoint [1] 304353 0
Clinical laboratory tests will be drawn at the screening visit, clinic check-in , and at end of study (2 days after patch removal).

Vital signs (heart rate , blood pressure, respiratory rate, and oxygen saturation) will be measured at the screening visit, before patch application, and 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 60, 72, and 84 hours after patch application. Then before patch removal (i.e. 96 hours after patch application), 8, 16, 24, 32, and 40 hours after patch removal

Skin irritation assessments will be performed at 1 hour and 24 hour after patch removal

ECG recordings will be taken at screening visit, clinic check-in, and end of study (2 days after patch removal).

Cardiac telemetry will start 8 hours before patch application and continue until 12 hours after patch removal.

Physical exams will be conducted at screening visit, clinic check-in, and end of study (2 days after patch removal).

Primary outcome [2] 304354 0
To evaluate the amount of liquid required during the hydration regiment to minimize or avoid the occurrence of bradycardia and/or hypotension as measured via blood pressure monitor.

Each subject will be given the specified amount of liquid as stipulated by their cohort assignment. The site staff will closely monitor each subject's water intake to ensure the specified volume is taken.
Timepoint [2] 304354 0
Liquid intake will be assessed at the following timepoints:
Cohort 1: 12 hours after patch application
Cohort 2, 3, 4, 5: 6 hours after patch application.

Blood pressure readings will be measured at the screening visit, before patch application, and 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 60, 72, and 84 hours after patch application. Then before patch removal (i.e. 96 hours after patch application), 8, 16, 24, 32, and 40 hours after patch removal.
Secondary outcome [1] 341710 0
To assess the pharmacokinetic profile of the DMTS as assessed by determining the pharmacokinetic parameters (Tmax, Cmax, AUC, and half-life) via blood samples.
Timepoint [1] 341710 0
Blood levels will be evaluated at predose and 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 60, 72, and 84 hours after application, before patch removal , 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 32, and 40 hours after patch removal.
Secondary outcome [2] 341711 0
To assess the sedation effect of dexmedetomidine as per the original Wilson sedation scale.
Timepoint [2] 341711 0
Sedation levels will be assess 1, 2, 3, 4, 6, 8, 10, 12, 24, 26, 28, 30, 32, 36, 48, 50, 52, 54, 56, 60, 72, and 84 hours after patch application, before patch removal, 8, 16, 24, 32, and 40 hours after patch removal.
Secondary outcome [3] 341712 0
To assess the adhesion of the DMTS by assessing the percentage of area the patch adheres to. This will be done via visual inspection by study staff.
Timepoint [3] 341712 0
Patch adhesion will be assessed at 6, 12, 24, 48, and 72 hours after patch application and immediately prior to patch removal.
Secondary outcome [4] 341714 0
To assess the dermal tolerability of the DMTS through assessments of skin irritation via the modified Draize scoring system.
Timepoint [4] 341714 0
Dermal tolerability will be assessed at at 1 hour and 24 hours after patch removal.

Eligibility
Key inclusion criteria
1. Healthy male or female subjects 18 to 45 years of age, inclusive.
2. Subjects must be non-smokers for at least 1 year prior to screening.
3. Body mass index (BMI) within the range of 18.0 to 38.0 , inclusive, and a weight of at least 50 kilograms.
4. Free of any dermatologic conditions, excessive hair, skin allergies, or sensitivities that may compromise the subject’s ability to wear the investigational product at any of the application sites for the specified duration of treatment.
5. Female subjects of childbearing potential must be practicing abstinence or using and willing to continue using a medically acceptable form of contraception for at least 1 month prior to screening (at least 3 months for oral contraceptives) and for at least 30 days after the last study drug administration. Female subjects of non-childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy, a bilateral tubal ligation and/or a bilateral oophorectomy (as determined by medical history). Male subjects who are not surgically sterile and have female partners of childbearing potential must ensure that they and their partners use the methods of contraception outlined above.
6. Female subjects must have a negative pregnancy test at screening and prior to dosing.
7. Must be able to speak, read, and understand English sufficiently to understand the nature of the study, to provide written informed consent, and to allow completion of all study assessments.
8. Must understand and provide written informed consent, prior to the initiation of any protocol-specific procedures.
9. Must be willing and able to abide by all study requirements and restrictions.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. A history or presence of drug or alcohol dependence (excluding caffeine), including subjects who have ever been in a drug rehabilitation program based on medical history of the past 10 years.
2. Clinically significant abnormalities as judged by the investigator or designee and determined by physical examination , medical history, 12-lead electrocardiogram , vital signs, laboratory values, including serum kidney and liver function tests.
3. Presence and/or history of postural hypotension (determined through examination by the investigator or designee), or recent history of severe dizziness or fainting on standing.
4. Subjects with a history of seizures, asthma (except for childhood asthma which has been asymptomatic for greater than or equal to 10 years), or obstructive pulmonary disease.
5. Presence or history of any of the following disorders that are deemed clinically significant by the investigator or designee: a psychiatric disorder (including suicidal ideation and behaviour), organic brain disorder, or seizure disorder.
6. Presence or history of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including ulcers or gastrointestinal bleeding), endocrine, immunologic, dermatologic, neurologic, oncologic, psychiatric disease, or any other condition, which, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
7. Abnormality (for example, scar, tattoo) or unhealthy skin (for example, burns, wounds) at the application site, according to examination by the investigator at screening, admission to the clinic, or prior treatment period of the study.
8. An existing chronic skin disease or history of skin disease at the application site within the 30 days prior to screening.
9. Use of any drugs containing estrogens within 30 days prior to study drug administration and throughout the study.
10. Use of any prescription drug (except acceptable forms of birth control) within 14 days prior to study drug administration and throughout the study.
11. Use of any prescription or non-prescription product containing any sympathomimetic amine (for example, pseudoephedrine, phenylephrine, and others commonly found in cold preparations) within 14 days prior to study drug administration and throughout the study.
12. Use of any natural health products (except vitamin or mineral supplements) within 14 days prior to study drug administration and throughout the study, unless in the opinion of the investigator or designee, the product will not interfere with the study procedures or data integrity, or compromise the safety of the subject.
13. Use of a non-prescription drug within 7 days prior to study drug administration; subjects who have taken over-the-counter medications, other than those described above, may still be entered into the study, if in the opinion of the investigator or designee, the medication received will not interfere with the study procedures or data integrity, or compromise the safety of the subject.
14. Positive test result for drugs of abuse at screening or prior to study drug dosing.
15. Positive alcohol test at screening or prior to study drug dosing.
16. Female subjects who are currently pregnant or lactating or who are planning to become pregnant within 30 days of last study drug administration.
17. History of allergy or hypersensitivity to dexmedetomidine or dexmedetomidine hydrochloride.
18. Positive for hepatitis B, hepatitis C, or the human immunodeficiency virus (HIV).
19. Donation of blood or loss of blood (greater than 100 mL) within 30 days prior to study drug administration.
20. Subject has a personal responsibility or already confirmed appointment(s) or court date(s) that would in any way prevent him/her from meeting the time commitments and visits required by the study.
21. Treatment with any investigational drug, device, or biologic within 30 days prior to study drug administration.
22. A subject who, in the opinion of the investigator or designee, is considered unsuitable for study entry and/or is unlikely to comply with the study protocol for any reason.

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)
Allocation is not concealed.
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
There are 5 cohorts in the study. Each cohort will receive 2 patches. Each cohort will drink a different volume of liquid:
Cohort 1 will drink 4 litres of liquid over a 14 hour period.
Cohort 2 will drink 4 litres of liquid over an 8 hour period.
Cohort 3 will drink 3 litres of liquid over an 8 hour period
Cohort 4 will drink 2 litres of liquid over an 8 hour period.
Cohort 5 subjects will receive a hydration regimen determined to be acceptable based on findings from Cohorts 2 - 4. The Safety Monitoring Committee will review the findings and a decision will be made when the Safety Monitoring Committee meets after the completion of Cohort 4.

A Safety Monitoring Committee will meet after the completion of each cohort to review the safety data collected. The next cohort will only occur after this meeting and if the Safety Monitoring Committee deemed the dose and hydration regimen safe and well tolerated.


After the 4 day patch application, there is a 2 day wash-out period.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
17/01/2018
Date of last participant enrolment
Anticipated
18/03/2018
Actual
3/04/2018
Date of last data collection
Anticipated
25/03/2018
Actual
9/04/2018
Sample size
Target
36
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 9678 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 18444 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 298326 0
Commercial sector/Industry
Name [1] 298326 0
Teikoku Pharma USA Inc.
Country [1] 298326 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services Pty Ltd
Address
88 Jephson Street
Toowong, QLD 4066
Country
Australia
Secondary sponsor category [1] 297442 0
Commercial sector/Industry
Name [1] 297442 0
Teikoku Pharma USA Inc.
Address [1] 297442 0
1718 Ringwood Avenue
San Jose, CA 95131
Country [1] 297442 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299319 0
Bellberry
Ethics committee address [1] 299319 0
Ethics committee country [1] 299319 0
Australia
Date submitted for ethics approval [1] 299319 0
08/11/2017
Approval date [1] 299319 0
19/12/2017
Ethics approval number [1] 299319 0
2017-11-838

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

Contacts
Principal investigator
Name 80038 0
Dr Lara Hatchuel
Address 80038 0
Linear Clinical Research
QE11 Medical Centre
Hospital Avenue
Nedlands, WA 6009
Country 80038 0
Australia
Phone 80038 0
+61 1300546327
Fax 80038 0
Email 80038 0
lhatchuel@linear.org.au
Contact person for public queries
Name 80039 0
James Song
Address 80039 0
Teikoku Pharma USA Inc.
1718 Ringwood Avenue
San Jose, CA 95131
Country 80039 0
United States of America
Phone 80039 0
+1 408 501 1821
Fax 80039 0
Email 80039 0
jsong@teikokuussa.com
Contact person for scientific queries
Name 80040 0
James Song
Address 80040 0
Teikoku Pharma USA Inc.
1718 Ringwood Avenue
San Jose, CA 95131
Country 80040 0
United States of America
Phone 80040 0
+1 408 501 1821
Fax 80040 0
Email 80040 0
jsong@teikokuussa.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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