Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001448538p
Ethics application status
Submitted, not yet approved
Date submitted
4/11/2024
Date registered
13/12/2024
Date last updated
13/12/2024
Date data sharing statement initially provided
13/12/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
The Pharmacokinetics and the Effect of Extended-release Thioguanine Tablets on Symptoms in Adults with Ulcerative Colitis.
Scientific title
Concentrations of Thioguanine and its metabolite 6-TGN in Blood and Colon Tissue Samples and the Drug Effect in Active Ulcerative Colitis Patients Administered Extended-release Thioguanine tablets
Secondary ID [1] 313304 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 335647 0
Active Ulcerative Colitis 335720 0
Condition category
Condition code
Oral and Gastrointestinal 332201 332201 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of thioguanine by extended-release oral tablets once daily, Cohort 1 has 6 participants who will receive 20mg for 14 weeks. If there is evidence of efficacy and no significant toxicity after 14 weeks of thioguanine administration in cohort 1, a second cohort of 6 participants will start, after Day 99 in cohort 1, and receive 10 mg daily for 14 weeks. Adherence monitored by product return, and pharmacokinetics on day 1 and day 99.
Intervention code [1] 329877 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339786 0
Change in inflammatory bowel disease symptoms
Timepoint [1] 339786 0
SCCAI at days 1, 8, 15, 22, and 29 post-commencement of thioguanine tablets.
Primary outcome [2] 339787 0
Change in colitis activity determined by endoscopic appearance
Timepoint [2] 339787 0
Day 99
Secondary outcome [1] 441330 0
The pharmacokinetics of thioguanine and its active metabolites 6-thioguanine nucleotides including AUC, Cmax, Tmax, Clearance and half-life
Timepoint [1] 441330 0
Blood samples drawn at 30 min, 1, 2, 4, and 6 hours and 24 post thioguanine administration on days 1 and 99 plus 30 hours on Day 99. Colonoscopy for disease activity by Mayo and UCEIS (ulcerative colitis endoscopic index of severity) scores at baseline and on day 99.
Secondary outcome [2] 441667 0
Safety signal monitoring
Timepoint [2] 441667 0
Weekly until Day 99
Secondary outcome [3] 442594 0
Blood concentrations of 6-TGN
Timepoint [3] 442594 0
On Day 1 at pre-dose, 30 minutes, 1, 2, 4, 6, and 24 post-dose
Secondary outcome [4] 442595 0
Colonic and rectal concentrations of 6-TGN
Timepoint [4] 442595 0
At steady-state at 14 weeks, with samples taken pre-dose from throughout the colon and rectum

Eligibility
Key inclusion criteria
Patients with active ulcerative colitis
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe extensive colitis.
2. Hospitalization for exacerbation of UC requiring intravenous (IV) steroids within 12 weeks of screening
3. A deficient (homozygous or heterozygous) Thiopurine S-methyl transferase (TPMT) enzyme activity or Nudix hydrolase 15 (NUDT15) genotype
4. Gastrointestinal infection
5. Previous exposure to TG and did not respond
6. Previous exposure to AZA and MP within 4 weeks prior to Day 1
7. Chronic hepatitis or abnormal liver biochemistry

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/01/2025
Actual
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
6/10/2025
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment outside Australia
Country [1] 26671 0
New Zealand
State/province [1] 26671 0

Funding & Sponsors
Funding source category [1] 317752 0
Commercial sector/Industry
Name [1] 317752 0
Douglas Pharmaceuticals
Country [1] 317752 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Douglas Pharmaceuticals
Address
Country
New Zealand
Secondary sponsor category [1] 320073 0
None
Name [1] 320073 0
Address [1] 320073 0
Country [1] 320073 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316442 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 316442 0
Ethics committee country [1] 316442 0
New Zealand
Date submitted for ethics approval [1] 316442 0
14/11/2024
Approval date [1] 316442 0
Ethics approval number [1] 316442 0

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

Contacts
Principal investigator
Name 137902 0
Prof Murray Barclay
Address 137902 0
Barclay Gastroenterology, 53 Straven Road, Christchurch 8011
Country 137902 0
New Zealand
Phone 137902 0
+64 272127334
Fax 137902 0
Email 137902 0
[email protected]
Contact person for public queries
Name 137903 0
Murray Barclay
Address 137903 0
Barclay Gastroenterology, 53 Straven Road, Christchurch 8011
Country 137903 0
New Zealand
Phone 137903 0
+64 272127334
Fax 137903 0
Email 137903 0
[email protected]
Contact person for scientific queries
Name 137904 0
Murray Barclay
Address 137904 0
Barclay Gastroenterology, 53 Straven Road, Christchurch 8011
Country 137904 0
New Zealand
Phone 137904 0
+64 272127334
Fax 137904 0
Email 137904 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: The data will belong to Douglas Pharmaceuticals who will make this decision later



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.