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Trial registered on ANZCTR


Registration number
ACTRN12615000127505
Ethics application status
Approved
Date submitted
28/10/2014
Date registered
11/02/2015
Date last updated
8/01/2020
Date data sharing statement initially provided
8/01/2020
Date results information initially provided
8/01/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
a phase I, Open-label, Pharmacokinetic Study of Nebivolol Hydrochloride in Healthy Chinese Volunteers
Scientific title
A phase I, Open label, Single-center, Dose-increasing Study to Determine the Pharmacokinetics of Single and Repeated oral administration of Nebivolol Hydrochloride in Healthy Chinese Volunteers
Secondary ID [1] 285554 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 293373 0
Condition category
Condition code
Cardiovascular 293658 293658 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For single dose study, volunteers will be assigned to 3 treatment groups of Nebivolol Hydrochloride: 5, 15, 30mg. After a 10-hour overnight fast, volunteers will receive a single dose of Nebivolol Hydrochloride oral tablet at approximately 8 a.m. on the following morning with 200mL water.
For repeated dose study, volunteers will received a single dose of Nebivolol Hydrochloride oral tablet 10mg at approximately 8 a.m. for 7 consecutive days.
Physical examinations, routine laboratory test(i.e., serum chemistry. hemotalogy and urinalysis), electrocardiogram, blood pressure and heart rate will be measured,adverse events will be recorded throughout the trial.
Intervention code [1] 290500 0
Treatment: Drugs
Comparator / control treatment
No control treatment for single dose study. Placebo control treatment for repeated dose study. The placebo tablets do not contain nebivolol. Other ingredients in the placebo tablet are exactly the same with test nebivolol tablets.
Control group
Placebo

Outcomes
Primary outcome [1] 293470 0
Pharmacokinetic of nebivolol enantiomers
Timepoint [1] 293470 0
For single dose study, blood will be sampled pre-dose, and 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 26h, 48h, 72h, 96h, 120h, 268h, 240h.
For repeated dose study, blood samples will be collected at the following timepoints: pre-dose; 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h after the first consecutive dose;before the 5th,6th,7th consecutive dose; 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 26h, 48h, 72h, 96h, 120h, 268h, 240h after the 7th consecutive dose.
The concentrations of nebivolol enantiomers are determined with HPLC-MS/MS.
The pharmacokinetic parameters of nebivolol enantiomers are calculated by phoenix winnolin sofeware.
Primary outcome [2] 293471 0
Assess the impact of CYP2D6 genotype on the pharmacokinetic behavior of nebivolol enantiomers.

The assessment will be performed after all the pharmacokinetic parameters in this study are calculated.
Timepoint [2] 293471 0
Genotype test of CYP2D6 will be performed at screening. Volunteers with CYP2D6*1*1 or CYP2D6*10*10 will be involved in this study. Pharmacokineitc profile difference will be evaluated between the two genotypes within dose group and between dose groups.
Secondary outcome [1] 311120 0
Safety: Adverse events (including bradycardia, Low blood pressure, dizziness and headache), clinical laboratory data(i.e. serum chemistry, hematology and urinalysis), vital signs, electrocardiogram(ECG), ventilation status, physical exam.
Adverse events will be monitored throughout the study based on spontaneous reports by volunteers, questioning by investigators, physical examinations, ECG results, vital signs and clinical test analysis. Adverse events information will be recorded in terms of intensity (mild, moderate, or severe), duration, outcome, and relationship to the study drug.
Timepoint [1] 311120 0
Physical examinations and routine laboratory profiles(i.e., serum chemistry. hemotalogy and urinalysis) will be performed before and 24h after the administration during the single dose study; and on day 1,2,5,8 pre-dose during the repeated dose study.
Holter(24h dynamic electrocardiogram) monitoring will be performed on the screening visit. 4 hour Holter will be performed after every dose.
Blood pressure and heart rate will be measured pre- and 2h, 4h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 168h, 240h pose-dose for the single and the last repeated dose as well as pre- and 2h, 4h, 6h post-dose on day 1 to 6 during the repeated dose study.
ECG will be measured pre- and 24h post-dose and on day 4 during single dose study, and before dose on day1, 2, 5, 7, 8,10 during the repeated dose study.
Volunteers will be instructed to come back for a safety evaluation on vital signs and physical examinations 1 week after the last blood sample is collected.

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, heart rate and laboratory test results(hematology, blood biochemistry, hepatic function, and urinalysis), negative results on HIV and hepatitis types B and C testing)
Genotype of CYP2D6 is *1*1(wild) or *10*10(Homozygous mutant)
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. weight less than 50kg, weight index less than 19 or more than 24;
2. low blood pressure history or blood pressur <90/60mmHg;
3. bradycardia, sinus arrest, sinoatrial block, atrioventricular blocker, 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, tape or foods;
7.use of prescription or over-the-counter medication including herbal products within 4 week 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)

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)
For single dose study, there is no randomisation.
For repeated dose study, subjects will be assigned to treatment with nebivolol or placebo in accordance with the randomisation schedule.Allocation is concealed by central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation schedule created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
The first part of the study(single dose study) is a open, dose increasing study without control group.This part of the study will start with low dose level, then move to high dose level.Participants are assigned to receive one of three doses (5mg,15mg,30mg).

The second part of the study(repeated dose study) is a parallel study. During the study,one group receive repeated dose of Nebivolol Hydrochloride 10mg, another group receive placebo tablets, Masking will be used in the second part of the study only.
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/10/2014
Actual
23/10/2014
Date of last participant enrolment
Anticipated
Actual
13/01/2015
Date of last data collection
Anticipated
Actual
29/01/2015
Sample size
Target
67
Accrual to date
Final
67
Recruitment outside Australia
Country [1] 6441 0
China
State/province [1] 6441 0
peking

Funding & Sponsors
Funding source category [1] 290159 0
Hospital
Name [1] 290159 0
Fuwai hospital
Country [1] 290159 0
China
Primary sponsor type
Hospital
Name
Fuwai hospital
Address
beilishi roal 167#, Xicheng district, Beijing, 10037
Country
China
Secondary sponsor category [1] 288868 0
Commercial sector/Industry
Name [1] 288868 0
Changzhou Siyao Pharmaceuticals Co.,Ltd
Address [1] 288868 0
Meilong Ba,Changzhou,Jiangsu Province,213004
Country [1] 288868 0
China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291869 0
the ethics and research committees in Fuwai hospital
Ethics committee address [1] 291869 0
beilishi road 167#, Xicheng district, Beijing, 100037
Ethics committee country [1] 291869 0
China
Date submitted for ethics approval [1] 291869 0
Approval date [1] 291869 0
17/09/2014
Ethics approval number [1] 291869 0

Summary
Brief summary
The purpose of this study is to explore the pharmacokinetic property, pharmacogenetic property as well as the safety and tolerance of Nebivolol Hydrochloride in Chinese healthy volunteers and provide important information for phase II study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52346 0
Prof Lei Tian
Address 52346 0
the Key Laboratory of Clinical Trial Research in Cardiovascular Drugs,Fuwai Hospital,beilishi road,167#,Xicheng district, Beijing, 100037
Country 52346 0
China
Phone 52346 0
+86 10-88398547
Fax 52346 0
Email 52346 0
[email protected]
Contact person for public queries
Name 52347 0
Lei Tian
Address 52347 0
the Key Laboratory of Clinical Trial Research in Cardiovascular Drugs,Fuwai Hospital,beilishi road,167#,Xicheng district, Beijing, 100037
Country 52347 0
China
Phone 52347 0
+86 10-88398547
Fax 52347 0
Email 52347 0
[email protected]
Contact person for scientific queries
Name 52348 0
Lei Tian
Address 52348 0
the Key Laboratory of Clinical Trial Research in Cardiovascular Drugs,Fuwai Hospital,beilishi road,167#,Xicheng district, Beijing, 100037
Country 52348 0
China
Phone 52348 0
+86 10-88398547
Fax 52348 0
Email 52348 0
[email protected]

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 Supporting Document Provided



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