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Trial registered on ANZCTR


Registration number
ACTRN12620000211965
Ethics application status
Approved
Date submitted
27/01/2020
Date registered
20/02/2020
Date last updated
20/02/2020
Date data sharing statement initially provided
20/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
To Assess the Effectiveness, Safety, and Tolerability of Oral Docarpamine in Patients with Refractory Ascites due to Liver Cirrhosis
Scientific title
A Phase 2a Open-Label Study Assessing the Effectiveness, Safety, and Tolerability of Oral
Docarpamine in Patients with Refractory Ascites due to Liver Cirrhosis
Secondary ID [1] 300146 0
MP-0128-001
Universal Trial Number (UTN)
Trial acronym
DREAM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver Cirrhosis 315676 0
Condition category
Condition code
Oral and Gastrointestinal 313982 313982 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will assess the effect of Docarpamine (DCP) treatment on ascites formation in cirrhotic subjects with Refractory Ascites (RA), by examining the frequency of large volume paracentesis (LVP) and the volume of ascitic fluid drained. All subjects will participate in a 90-day open-label treatment period, followed by a 90-day follow-up. Ascites history (relevant medications, LVP dates, and volume of drained fluid) for the 90 days prior to treatment and the 90 days after treatment will be collected and used for comparison with on-treatment frequency and volume.
Treatment with DCP will be initiated within 3 days of each subject’s most recent LVP, and as close to LVP as is feasible. Subjects will receive the first dose of study drug while in the clinic, so that safety observations and pharmacokinetic sampling can be conducted. Subsequent dosing will be done by the subject outside of the clinic.

DCP 750 mg granules, orally administered three times daily, approximately every 8 hours. If a dose is missed, the next dose should be taken as soon as possible. There should be at least 5 hours between doses. Two doses should never be taken at the same time.

Intervention code [1] 316431 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Active

Outcomes
Primary outcome [1] 322393 0
Total volume of ascetic fluid drained as assessed by site procedural source documentation
Timepoint [1] 322393 0
Throughout the study
Secondary outcome [1] 378318 0
Safety & tolerability will be assessed by Medical History, Physical Exam, Ascites Grade, Hepatic Encephalopathy, 12-lead ECG, vital signs, hematology, blood chemistry, liver function, coagulation tests, urine test and as well as assessing AEs, and concomitant medications and procedures.
Timepoint [1] 378318 0
Performed at baseline, at each LVP visit and at 7 ± 1 day, 14 ± 2 days, 21 ± 4 days, 28 ± 4 days, 56 ± 7 days, 90 ±7 days, and 120 ± 7 days. LVP visits that fall within a scheduled visit range will serve as that visit. Telephone check-ins will be performed on days 2, 3, 4, 5, 6, 42 ± 4 and 70 ± 4. After the first dose, vital signs and 12-lead ECG will be captured at 1 hour ± 5 minutes, 2 hours ± 10 minutes, 3 hours ± 10 minutes, and 6 hours ± 15 minutes.

24-hour urine specimens will be collected at baseline, 28 ±4 days, 56 ±7 days, and 90 ±7 days.
Secondary outcome [2] 379683 0
Docarpamine pharmacokinetics.

Parameters to be examined: Cmax, AUCtau, Tmax
Timepoint [2] 379683 0
PK samples will be obtained to measure plasma-free dopamine, with sampling on Day 1 (pre-dose, 1 hours ± 5 minutes, 2 hours ± 10 minutes, 3 hours ± 10 minutes, and 6 hours ± 15 minutes), and then at every visit during the treatment period about 24hour urine specimens.


Eligibility
Key inclusion criteria
1. Patients 18 years to 70 years of age.
2. Documented cirrhosis of the liver.
3. Refractory ascites, defined as ascites not manageable with diuretics and diet restriction, managed with periodic large volume therapeutic paracentesis.
4. Patients must have therapeutic paracenteses in the 3 days prior to enrollment and a documented minimum of 3 additional therapeutic paracenteses in the 90 days prior to enrollment, with at least 1 every 30 days.
5. Outpatient, with expected survival of at least 6 months.
6. Willing and able to complete an informed consent form.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Ascites due to any cause other than cirrhosis such as malignant ascites.
2. Existing or planned placement of TIPS or other surgical shunts.
3. Active bacterial infection.
4. Scheduled organ transplantation within the next 6 months.
5. Change in diuretics schedule within 30 days prior to initiation of treatment.
6. MELD-Na Score of greater than 25 (based on the most recent bloodwork per medical records and within 30 days of screening for participation).
7. Serum creatinine greater than 2 mg/dL (based on the most recent bloodwork per medical records and within 30 days of screening for participation).
8. Serum bilirubin greater than 5 mg/dL (based on the most recent bloodwork per medical records and within 30 days of screening for participation)..
9. INR greater than 1.5 (based on the most recent bloodwork per medical records and within 30 days of screening for participation)..
10. Hepatocellular Carcinoma BCLC stage C or above.
11. Current or recent (within 3 months of consent) renal dialysis.
12. Hepatic encephalopathy grade 3 or 4.
13. Pheochromocytoma or hypertrophic obstructive cardiomyopathy.
14. Current or recent treatment (within 7 days) with octreotide, midodrine, vasopressin, dopamine or other vasopressors.
15. Current or recent treatment (within 21 days) with MAO inhibitors, tricyclic antidepressants, phenytoin, haloperidol or haloperidol-like drugs, or phenothiazines such as prochlorperazine.
16. Episode of spontaneous bacterial peritonitis or gastrointestinal hemorrhage, or any acute decompensation within 30 days of enrollment.
17. Severe cardiovascular disease such as CHF, advanced arteriosclerosis, coronary insufficiency, tachyarrhythmia, or uncontrolled hypertension above 160/100.
18. Known or suspected extra-hepatic malignancy (other than skin cancer and in-situ cancers), unless adequately treated.
19. Pregnant females, females anticipating pregnancy during study period, or breastfeeding.
20. Known allergy or hypersensitivity to dopamine or DCP.
21. Any severe comorbidity that in the opinion of the Investigator would disallow safe participation in the trial.
22. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 90 days of consent.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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)
NSW,QLD,SA,WA
Recruitment hospital [1] 15591 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 15592 0
Gold Coast Hospital - Southport
Recruitment hospital [3] 15593 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 15594 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 28991 0
2747 - Kingswood
Recruitment postcode(s) [2] 28992 0
4215 - Southport
Recruitment postcode(s) [3] 28993 0
5000 - Adelaide
Recruitment postcode(s) [4] 28994 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 304581 0
Commercial sector/Industry
Name [1] 304581 0
Martin Pharmaceuticals Australia Pty Ltd.
Address [1] 304581 0
58 Gipps Street, Collingwood, VIC 3066, Australia
Country [1] 304581 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Martin Pharmaceuticals Australia Pty Ltd.
Address
58 Gipps Street, Collingwood, VIC 3066, Australia
Country
Australia
Secondary sponsor category [1] 304867 0
None
Name [1] 304867 0
Address [1] 304867 0
Country [1] 304867 0
Other collaborator category [1] 281130 0
Commercial sector/Industry
Name [1] 281130 0
Novotech (Australia) Pty Limited
Address [1] 281130 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 281130 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305007 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 305007 0
41 Victoria Parade, Fitzroy VIC 3065
Ethics committee country [1] 305007 0
Australia
Date submitted for ethics approval [1] 305007 0
19/11/2019
Approval date [1] 305007 0
06/12/2019
Ethics approval number [1] 305007 0

Summary
Brief summary
This study is an open-label, single-arm study in which each subject will serve as his/her own control. The study will assess the effect of DCP treatment on ascites formation in cirrhotic subjects with RA, by examining the frequency of LVP and the volume of ascitic fluid drained. All subjects will participate in a 90-day open-label treatment period, followed by a 90-day follow-up. Ascites history (relevant medications, LVP dates, and volume of drained fluid) for the 90 days prior to treatment and the 90 days after treatment will be collected and used for comparison with on-treatment frequency and volume.
Treatment with DCP will be initiated within 3 days of each subject’s most recent LVP, and as close to LVP as is feasible. Subjects will receive the first dose of study drug while in the clinic, so that safety observations and pharmacokinetic sampling can be conducted. Subsequent dosing will be done by the subject outside of the clinic.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98946 0
Dr Edmund Tse
Address 98946 0
Royal Adelaide Hospital, Port Rd Adelaide SA 5000
Country 98946 0
Australia
Phone 98946 0
+61 423 080 487
Fax 98946 0
Email 98946 0
Edmund.Tse@sa.gov.au
Contact person for public queries
Name 98947 0
Ms Joanne Morgan
Address 98947 0
Royal Adelaide Hospital, Port Rd Adelaide SA 5000
Country 98947 0
Australia
Phone 98947 0
+61 87074 2190
Fax 98947 0
Email 98947 0
joanne.morgan@sa.gov.au
Contact person for scientific queries
Name 98948 0
Ms Ann C. Tunstall
Address 98948 0
Martin Pharmaceuticals , 233 Broadway 17th Floor, New York, NY 10279, USA
Country 98948 0
United States of America
Phone 98948 0
+1 7039818338
Fax 98948 0
Email 98948 0
ann@martinpharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
None
What supporting documents are/will be available?
No other documents available
Summary results
No Results