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Trial registered on ANZCTR


Registration number
ACTRN12617000031369
Ethics application status
Approved
Date submitted
14/12/2016
Date registered
9/01/2017
Date last updated
22/01/2020
Date data sharing statement initially provided
22/01/2020
Date results information initially provided
22/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetic and safety study of HTD1801 and its components
Scientific title
A singe-blind, randomised, triple cross-over, single-dose pharmacokinetic and safety study of HTD1801 and its components.
Secondary ID [1] 290717 0
HighTide Biopharma Pty Ltd
Protocol number: 1801.PCT001
Universal Trial Number (UTN)
U1111-1190-6978
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Sclerosing Cholangitis (PSC) 301290 0
Condition category
Condition code
Oral and Gastrointestinal 301043 301043 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 301044 301044 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The treatments are HTD1801, 1500mg, BBR 1000mg and UDCA 1000mg, one oral dose of each treatment. There will be a washout period of at least 7 days and up to 10 days..
Participants will be admitted to the treatment unit where the investigational products will be administered.
Intervention code [1] 296616 0
Treatment: Drugs
Comparator / control treatment
Berberine (BBR), 1000mg oral one dose
Ursodeoxycholic acid (UDCA), 1000mg, oral one dose
Control group
Active

Outcomes
Primary outcome [1] 300465 0
Primary endpoint:
AUC0-t. This is assessed by obtaining the plasma concentration of each investigational product.
Timepoint [1] 300465 0
This is a PK and safety study. PK measures are recorded on 12 occasions after each dosing. The post dose time points are - 30minutes, 1hr, 2hr, 3hr, 4gr, 6hr, 8hr, 12hr, 16hr, 24hr, 30hr, 36hr.
Secondary outcome [1] 330027 0
Secondary endpoint:
Tmax
Timepoint [1] 330027 0
Tmax is measure through serum sampling. Blood measures are recorded prior to dosing and on 12 occasions after each dosing. Safety parameters are measured through out the study. The time points are:
Pre dose, post dose measures are - 30minutes, 1hr, 2hr, 3hr, 4hr, 6hr, 8hr, 12hr, 16hr, 24hr, 30hr and 36hr.
Secondary outcome [2] 330298 0
Cmax.
Timepoint [2] 330298 0
Cmax is measure through serum sampling. Blood measures are recorded prior to dosing and on 12occasions after each dosing. The time points are:
Pre dose, post dose measures are - 30minutes, 1hr, 2hr, 3hr, 4hr, 6hr, 8hr, 12hr, 16hr, 24hr, 30hr and 36hr.
Secondary outcome [3] 330299 0
T1/2
Timepoint [3] 330299 0
T1/2 is measure through serum sampling. Blood measures are recorded prior to dosing and on 12occasions after each dosing. The time points are:
Pre dose, post dose measures are - 30minutes, 1hr, 2hr, 3hr, 4hr, 6hr, 8hr, 12hr, 16hr, 24hr, 30hr and 36hr.
Secondary outcome [4] 330300 0
Adverse Events (AES). AEs will be measured through communication with the participants and through performing physical examinations.
Timepoint [4] 330300 0
AEs will be monitored .at pre dose and the following post dose time points - 1hr, 4hr, 8hrs, 12hr, 16hrs, 24hrs, 30hrs and 36hrs. Physical examinations will be performed at pre dose and 1 day post dose.
Secondary outcome [5] 330301 0
Blood haematology. Components are:
Haemoglobin
Haematocrit
RBC Count
Platelets Count
WBC Count
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Timepoint [5] 330301 0
Blood haematology will be measure through serum sampling. Sampling will occur at the following timepoints - Pre dose, 1 day post dose.
Secondary outcome [6] 330302 0
Vital signs will be measured by measuring heart rate, blood pressure, respiratory rate and temperature.
Timepoint [6] 330302 0
Vital signs will be measured at pre dose and the following post dose time points - 1hr, 4hr, 8hrs, 12hr, 16hrs, 24hrs, 30hrs and 36hrs.
Secondary outcome [7] 330303 0
ECGs. The electrical activity of the heart will be measured.
Timepoint [7] 330303 0
ECGs will be performed at pre dose and the following post dose time points - 1hr, 4hr, 8hrs, 12hr, 16hrs, 24hrs, 30hrs and 36hrs.
Secondary outcome [8] 330432 0
Blood chemistry will be measured. Components are:
Urea
Creatinine
AST
ALT
Alkaline Phosphatase
Total Bilirubin
Timepoint [8] 330432 0
Blood chemistry will be measure through serum sampling. Sampling will occur at the following timepoints - Pre dose, 1 day post dose.

Eligibility
Key inclusion criteria
Males and females
18-45 years of age
BMI 20-35 kg/m2
No history of CV or any other major disease
No pathologies in blood haematology or chemistry
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
BP greater than or equal to 160/95
HR greater than or equal to 100bpm or less than or equal to 45 bpm
Significant cardiac arrhythmia
Untreated hypo- or hyperthyroidism
Clinically significant liver (greater than 3 times ULN) and/or kidney impairment
Inability to tolerate UDCA or BBR
Contraindications to BBR and UDCA
G6PD deficiency
Gastritis or gastric ulcers
Pregnancy
Any background medication or dietary supplements which might alter with
pharmacokinetic profile of IMP or active controls
Any other clinically meaningful condition, in the opinion of the investigator, which
would make participation potentially unsafe

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)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Latin square design will be used for this study
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Exploratory analyses will be made using ANCOVA.
No formal power calculation

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/02/2017
Actual
4/04/2017
Date of last participant enrolment
Anticipated
13/02/2017
Actual
9/06/2017
Date of last data collection
Anticipated
8/03/2017
Actual
11/07/2017
Sample size
Target
24
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7094 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 14850 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 295147 0
Commercial sector/Industry
Name [1] 295147 0
HighTide Biopharma Pty Ltd
Country [1] 295147 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 4, 88 Joseph ST
TOOWONG QLD 4066
Country
Australia
Secondary sponsor category [1] 293966 0
Commercial sector/Industry
Name [1] 293966 0
HighTide Biopharma Pty Ltd
Address [1] 293966 0
1 Melissa Street,
Mount Waverley, Vic 3149

Country [1] 293966 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296494 0
Bellberry Limited
Ethics committee address [1] 296494 0
129 Glen Osmond Road
Eastwood
South Australia 5063
Ethics committee country [1] 296494 0
Australia
Date submitted for ethics approval [1] 296494 0
07/12/2016
Approval date [1] 296494 0
23/03/2017
Ethics approval number [1] 296494 0
2017-02-131

Summary
Brief summary
This will be a single-blind, randomized, single-dose, triple-cross over (a Latin square design), single-centre study. 24 Subjects will be enrolled. Each subject will receive all three treatments in random order. At each administration day approximately 1/3 of subjects will receive treatment A, 1/3 treatment B, and 1/3 treatment C and this will switch around on the second administration day and then again on third administration day until all participants have been administered all three treatments.

Screening: Subjects will be screened for the study. Eligible subjects will return for the admission to the Unit within four (4) weeks following screening. All subjects will be instructed to maintain their lifestyle and background medications, if any.

Baseline: Subjects will be admitted to the Unit in the evening of Day -1. Blood draw to establish the baseline for all measured endpoints will be drawn in the morning of Day 0.

Randomisation: Following the completion of all baseline assessments and draws on Day 0, eligible subjects will be randomized so that approximately 1/3 of subjects will receive treatment A, 1/3 treatment B, and 1/3 treatment C. The first dose of study medication will be then promptly administered.

Drug administration and assessment periods: Each subject will receive a drug three times in random pre-determined order, single dose, separated by at least 14 days of washout. Following each administration, blood for PK and safety will be drawn and safety and tolerability assessments will be conducted over the ensuing 36 hours.

Final tolerability/safety assessment: Approximately seven (7) days following the administration of the last medication, the site will follow up over the phone with the subjects regarding any tolerability or safety issue; if clinically necessary, they could be invited back to the Unit for follow up tests or evaluation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71058 0
Dr Janet Wong
Address 71058 0
Nucleus Network
5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne
Victoria, 3004
Country 71058 0
Australia
Phone 71058 0
+ 613 9076 8900
Fax 71058 0
+ 613 9076 8911
Email 71058 0
businessdevelopment@nucleusnetwork.com.au
Contact person for public queries
Name 71059 0
Dr Steve Linberg
Address 71059 0
HighTide Biopharma Pty Ltd
1Melissa Street
Mount Waverley
Victoria 3149
Country 71059 0
Australia
Phone 71059 0
+61 7 3719 6000
Fax 71059 0
+61 7 3719 6011
Email 71059 0
slinberg@hightidebio.com
Contact person for scientific queries
Name 71060 0
Dr Steve Linberg
Address 71060 0
HighTide Biopharma Pty Ltd
Melissa Street
Mount Waverley
Victoria 3149
Country 71060 0
Australia
Phone 71060 0
+61 7 3719 6000
Fax 71060 0
Email 71060 0
slinberg@hightidebio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All publications and data analyses etc from the study would be generated by and delivered to HighTide. However the PI reviewed and signed off on both.


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.