Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000791235
Ethics application status
Approved
Date submitted
7/05/2018
Date registered
10/05/2018
Date last updated
27/05/2019
Date data sharing statement initially provided
25/02/2019
Date results provided
25/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of HM30181A on the Pharmacokinetics of Dabigatran
Scientific title
An Open-Label, Non-Randomized, Fixed Sequence Study in Healthy Volunteers to Evaluate the Effect of HM30181A on the Pharmacokinetics of Dabigatran
Secondary ID [1] 294786 0
KX-HM-001
Universal Trial Number (UTN)
U1111-1191-7304
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 307711 0
Condition category
Condition code
Cancer 306766 306766 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
As HM30181A is an inhibitor of P-gp, it may increase the bioavailability of orally administered drugs which are substrates of P-gp such as dabigatran.
The primary objective of this study is to determine the effect of multiple once-daily
doses of HM30181A on the single-dose pharmacokinetics of dabigatran. In addition, the study will estimate the duration of the effect on P-gp inhibition by HM30181A on dabigatran exposure by determining the PK of dabigatran at 2 and 4 weeks after the
administration of HM30181A.
Eligible participants will receive a single oral tablet of dabigatran 75mg and will provide blood samples for analysis for 48 hours post-dosing (Treatment Period 1). After at least a 7 day washout, Treatment Period 2 will start.
During Treatment Period 2, participants will receive daily oral doses of a 15mg HM30181A tablet for 3 days (Days 1, 2 and 3). One hour after the third dose they will receive a single oral tablet of dabigatran 75mg. Blood samples will be collected for Days 1-8.
On Day 17, they will have another single oral tablet of dabigatran 75mg with blood samples collected for 5 days post-dose.
On Day 31 they will have a final dose of a single oral tablet of dabigatran 75mg with blood samples collected for 48 hours post-dose.
There will be a followup phone call about 2 weeks after the last blood sample is collected.
Safety will be monitored regularly with laboratory tests, aPPT, recording of AEs, ECGs and vital signs. Participants will be resident at the Zenith Clinical Site for dosing (all doses will be under the direct supervision of study site staff) and days when multiple blood samples are required.
Intervention code [1] 301118 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305778 0
The primary endpoint will be area under the plasma concentration curve (AUC0-8) and maximum concentration (Cmax) of total dabigatran in the plasma after dabigatran etexilate administration in Treatment Period 1, and dabigatran etexilate administration on Day 3 after HM30181A in Treatment Period 2.
Timepoint [1] 305778 0
Blood samples for determination of plasma concentrations of total and unconjugated dabigatran will be collected on: Treatment Period 1: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours post-dose dabigatran etexilate
Treatment Period 2: Days 1, 2 and 3: pre-dose HM30181A. Days 3-8: pre-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48 and 120 hours post-dose Day 3 dabigatran etexilate
Days 17-22: pre-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48 and 120 hours post-dose Day 3 dabigatran etexilate
Days 31-33: re-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours post-dose Day 3 dabigatran etexilate
Secondary outcome [1] 346515 0
To investigate the duration of the effect of HM30181A on the single-dose pharmacokinetics of dabigatran. This will be achieved by comparing the AUC0-8 and Cmax of total dabigatran in the plasma after dabigatran etexilate administration in Treatment Period 1, with the AUC0-8 and Cmax of total dabigatran in the plasma after dabigatran etexilate administration on Days 17 and 31 (i.e. after HM30181A in Treatment Period 2)
Timepoint [1] 346515 0
Treatment Period 1: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours post-dose dabigatran etexilate
Treatment Period 2: The blood samples will be collected on Days 1, 2 and 3: predose HM30181A. Days 3-8: pre-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48 and 120 hours post-dose Day 3 dabigatran etexilate. Day 17: pre-dose dabigatran etexilate
Days 17-22: pre-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48 and 120 hours post-dose Day 3 dabigatran etexilate
Days 31-33: re-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours post-dose Day 3 dabigatran etexilate
Secondary outcome [2] 346516 0
To investigate the safety and tolerability of HM30181A and dabigatran when administered sequentially by review of AEs/SAEs, laboratory values (including aPPT), vital signs, results of physical examinations and ECGs
Timepoint [2] 346516 0
Assessments will be conducted at the following time-points:
AEs/SAEs: at each study site visit - Screening; Treatment Period 1: Baseline, Days 1, 2 and 3; Treatment Period 2: Baseline, Days 1, 2, 3, 4, 5, 8, 16, 17, 18, 19, 22, 30, 31, 32, 33; and follow-up phone call
Laboratory tests will be conducted at: Screening, Treatment Period 1 - Baseline and Day 3; Treatment Period 2 - Baseline, Days 5, 16, 19, 30 and 33.
aPPT tests will be conducted at: Screening, Treatment Period 1 - Baseline and Days 1- 3; Treatment Period 2 - Baseline, Days 3-5, 17-19, 31-33.
Vital signs will be conducted at: Screening, Treatment Period 1 - Baseline and Days 1- 3; Treatment Period 2 - Baseline, Days 1-5, 16-19, 30-33
Physical examinations at Screening, Treatment Period 1 - Baseline; Treatment Period 2 - Baseline, Days 16, 30 and 33
ECGs at Screening and Day 33
Secondary outcome [3] 346517 0
To determine the pharmacokinetics of HM30181 by determining its PK parameters including AUC0-24, Tmax, Cmax, Cmin, and T1/2.
Timepoint [3] 346517 0
The blood samples will be collected on:
- Days 1, 2 and 3: pre-dose HM30181A.
- Days 3-8: pre-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48 and 120 hours post-dose Day 3 dabigatran etexilate.
- Day 17: pre-dose dabigatran etexilate
Secondary outcome [4] 346700 0
To determine the pharmacokinetics of the M1 metabolite of HM30181 by determining its PK parameters including AUC0-24, Tmax, Cmax, Cmin, and T1/2.
Timepoint [4] 346700 0
The blood samples will be collected on:
- Days 1, 2 and 3: pre-dose HM30181A.
- Days 3-8: pre-dose dabigatran etexilate and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48 and 120 hours post-dose Day 3 dabigatran etexilate.
- Day 17: pre-dose dabigatran etexilate

Eligibility
Key inclusion criteria
Males aged at least 18 years and up to 55 years on day of consent; Creatinine clearance greater than or equal to 80 mL/min; non-smoker; in good health; Body mass index (BMI) greater than or equal to 18.0 and less than 30.0 kg/m2 at Screening; willing to adhere to the alcohol and caffeine restrictions
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
A history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases; an elevated prothrombin time (PT) or aPTT or platelet count below the lower limit of normal at Screening or Baseline; History of gastrointestinal bleeding, intracerebral bleeding or frequent nose-bleeds or active bleeding; prolonged QTc interval (QTc >450 ms) on ECG at Screening; history of drug or alcohol abuse or dependence; taking any prescription drug or herbal medicine or supplement within 2 weeks or 5 half-lives prior to dosing, whichever is longer, or vitamin supplement within 1 week prior to dosing; clinically significant drug allergy; surgery within 30 days prior or planned within 4 weeks after the study.

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)
Allocation is not concealed
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
Fixed sequence design
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Statistical analyses will be reported using summary tables, graphs, and data listings. Continuous variables will be summarized using the mean, standard deviation (SD), median, minimum, and maximum. Categorical variables will be summarized by counts and by percentage of subjects in corresponding categories.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/09/2018
Actual
17/10/2018
Date of last participant enrolment
Anticipated
15/01/2019
Actual
20/02/2019
Date of last data collection
Anticipated
11/04/2019
Actual
18/04/2019
Sample size
Target
20
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 10376 0
New Zealand
State/province [1] 10376 0
Otago

Funding & Sponsors
Funding source category [1] 299394 0
Commercial sector/Industry
Name [1] 299394 0
Athenex Inc
Country [1] 299394 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Athenex Inc
Address
20 Commerce Drive
Cranford
New Jersey 07016
Country
United States of America
Secondary sponsor category [1] 298672 0
Commercial sector/Industry
Name [1] 298672 0
Zenith Technology Corporation
Address [1] 298672 0
156 Frederick Street
Dunedin 9016
Country [1] 298672 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300297 0
Northern A HDEC
Ethics committee address [1] 300297 0
Ethics committee country [1] 300297 0
New Zealand
Date submitted for ethics approval [1] 300297 0
02/05/2018
Approval date [1] 300297 0
30/07/2018
Ethics approval number [1] 300297 0

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

Contacts
Principal investigator
Name 83194 0
Dr Christopher Jackson
Address 83194 0
Dunedin Hospital
Southern District Health Board
201 Great King Street
Dunedin 9016
Country 83194 0
New Zealand
Phone 83194 0
+64 3 474 0999 ext 9698
Fax 83194 0
Email 83194 0
[email protected]
Contact person for public queries
Name 83195 0
Linda Folland
Address 83195 0
Zenith Technology Corporation, Ltd.
156 Frederick Street
Dunedin 9016
Country 83195 0
New Zealand
Phone 83195 0
+64 3 477 9669
Fax 83195 0
Email 83195 0
[email protected]
Contact person for scientific queries
Name 83196 0
Wing-Kai Chan
Address 83196 0
Athenex Pharmaceuticals
19F., No.460, Sec. 4, Xinyi Rd., Xinyi Dist.
Taipei City 110
Country 83196 0
Taiwan, Province Of China
Phone 83196 0
+886 277039399
Fax 83196 0
Email 83196 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
At this stage the Sponsor does not plan to release IPD


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
SourceTitleYear of PublicationDOI
Dimensions AIOral paclitaxel with encequidar compared to intravenous paclitaxel in patients with advanced cancer: A randomised crossover pharmacokinetic study2021https://doi.org/10.1111/bcp.14886
N.B. These documents automatically identified may not have been verified by the study sponsor.