Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000207415
Ethics application status
Approved
Date submitted
30/11/2015
Date registered
16/02/2016
Date last updated
16/02/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase I, Open-Label, Pharmacokinetic Study of tolvaptan in healthy Chinese volunteers
Scientific title
A Phase 1, Open Label, Single-Center, Dose-increasing Study to Determine the Safety and Pharmacokinetics of Single and Repeated oral administration of tolvaptan in Healthy Chinese Volunteers
Secondary ID [1] 288028 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hyponatremia 296897 0
Condition category
Condition code
Cardiovascular 297127 297127 0 0
Other cardiovascular diseases
Metabolic and Endocrine 297662 297662 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This clinical trial was conducted at the phase I ward in fuwai hospital All doses supervised at study centre.
In single dose study, volunteers were assigned to 4 treatment groups of tolvaptan: 15, 30, 60 and 120mg. After a 10-hour overnight fast, volunteers received a single dose of tolvaptan orally at approximately 8 a.m. on the following morning (day 1) with 200mL water
In multiple dose study, volunteers were assigned to 2 treatment groups of tolvaptan: 30 and 60mg..After a 10-hour overnight fast, volunteers received a dose of tolvaptan orally(30 or 60mg) at approximately 8 a.m. on the following morning (day 1) with 200mL water, 3 days after first dose(day 4), volunteers of two groups received oral doses of tolvaptan (same as respective first dose) daily for 6 consecutive days.
Intervention code [1] 293354 0
Treatment: Drugs
Comparator / control treatment
.All treatment groups would have equal weight in this study.
Control group
Dose comparison

Outcomes
Primary outcome [1] 296746 0
Pharmacokinetics.
Pharmacokinetic parameters (Tmax, Cmax, t1/2, AUC, MRT, Cav, Cmin, Accumulation Index, Fluctuation%,etc)was calculated by the drug concentration data in plasma using non-compartment model (phoenix winnolin software).
Timepoint [1] 296746 0
For single dose study, blood will be sampled pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 144h, 216h, 288h and 432h after administration.
For multiple dose study, blood will be sampled
1) on day 1, at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h adn 72h after first dose;
2) pre-dose from day 4 to day 10;
3) on Day 10, at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h adn 72h after administration.
Secondary outcome [1] 319249 0
Safety was evaluated by adverse events, clinical laboratory data, vital signs, physical exam.
Timepoint [1] 319249 0
Adverse events(AEs) were monitored throughout the study based on spontaneous reports by volunteers, questioning by investigators, physical examinations.
Physical examinations was performed, blood pressure, heart rate and breath were measured 1) for single dose study, at pre-dose,1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h after administration and at 8:00AM on day 6, day 9, day 12, day 15, day 18; 2) for multiple dose study, at pre-dose, 1h, 2h, 4h, 8h, 12h, 24h, 48h after first dose; at pre-dose and 2h after dose on day 4 to day 10; at 24h, 48h, 72h after the last consecutive dose.
Electrocardiogram (ECG) was performed 1)at pre-dose, 6h, 12h and 24h after administration for single dose study; 2)at pre-dose, 6h, 12h, 24h after first dose; pre-dose on day 6 and day 10; 48h after the last consecutive dose for multiple dose study.
Clinical laboratory test(i.e., serum chemistry, hematology and urinalysis) was performed 1) at 24h after admimistration for single dose study; 2) at 24h after first dose, pre-dose on day 4 and day 8, 48h after the last consecutive dose for multiple dose study.
Secondary outcome [2] 319250 0
Pharmacodynamic, assessed using serum electrolyte, daily urine volume and daily fluid intake.
Timepoint [2] 319250 0
serum electrolyte(K, Na, Cl and Mg) was measured 1)at pre-dose , 2h, 4h, 6h, 8h, 12h, 24h, 48h after administration for single dose study; 2)at pre-dose, 2h, 4h, 6h, 8h, 12h, 24h after first dose; pre-dose on day 4, day 6, day 8 and day 10; 48h after the last consecutive dose for multiple dose study.
Urine volume and daily fluid intake was recorded 1) until 48h after administration for single dose study; 2)until 24h after the last consecutive dose for multiple dose study.

Eligibility
Key inclusion criteria
Body mass index between 19 and 24 kg/m^2, nonsmokers, thorax radiography and electrocardiography without abnormalities, normal values of BP and heart rate and laboratory test results(hematology, blood biochemistry, hepatic function, and urinalysis), negative results on HIV and hepatitis types B and C testing, negative on urine human chorionic gonadotrophin (HCG) test for the female.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. weight less than 50kg , body mass index less than 19 or body mass index more than 24
2.low blood pressure
3.bradycardia,sinus arrest, sinoatrial block, atrioventricular block, ectopic rhythm Holter monitoring ;
4.disease or disorders in hepatic, renal, respiratory, immune system and nervous system;
5.alcohol or drug abuse;
6.clinical significant allergies to drug or foods;
7.use of prescription or over-the-counter medication including herbal products within 4 weeks before study initiation;
8.donate blood or participated in other clinical trials within 3 months before enrollment in the study
9.positive results on HIV and hepatitis types B and C testing
10.abnormalities in laboratory test(hematology, blood biochemistry, hepatic function, and urinalysis)
11. urination disorder

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
Other
Other design features
The trial was carried out from low dose group to high dose group. Mutilple dose group was conducted after all single dose groups finished. There was one day or two interval between each group for the investigator to review the safety of the previous dose.
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
15/07/2011
Date of last participant enrolment
Anticipated
Actual
19/07/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
72
Accrual to date
Final
69
Recruitment outside Australia
Country [1] 7389 0
China
State/province [1] 7389 0
Beijing

Funding & Sponsors
Funding source category [1] 292479 0
Hospital
Name [1] 292479 0
Fuwai hospital
Country [1] 292479 0
China
Primary sponsor type
Hospital
Name
Fuwai hospital
Address
beilishi road 167#, Xicheng district, Beijing, 100037
Country
China
Secondary sponsor category [1] 291185 0
None
Name [1] 291185 0
Address [1] 291185 0
Country [1] 291185 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293944 0
the ethics and research committees in Fuwai hospital
Ethics committee address [1] 293944 0
Ethics committee country [1] 293944 0
China
Date submitted for ethics approval [1] 293944 0
Approval date [1] 293944 0
18/05/2011
Ethics approval number [1] 293944 0

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

Contacts
Principal investigator
Name 61870 0
Prof Lei Tian
Address 61870 0
Fuwai hospital, beilishi road 167#, xicheng district, Beijing, 100037
Country 61870 0
China
Phone 61870 0
+86 10-88398547
Fax 61870 0
Email 61870 0
[email protected]
Contact person for public queries
Name 61871 0
Lei Tian
Address 61871 0
Fuwai hospital, beilishi road 167#, xicheng district, Beijing, 100037
Country 61871 0
China
Phone 61871 0
+86 10-88398547
Fax 61871 0
Email 61871 0
[email protected]
Contact person for scientific queries
Name 61872 0
Lei Tian
Address 61872 0
Fuwai hospital, beilishi road 167#, xicheng district, Beijing, 100037
Country 61872 0
China
Phone 61872 0
+86 10-88398547
Fax 61872 0
Email 61872 0
[email protected]

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

Documents added manually
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