Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001178730
Ethics application status
Approved
Date submitted
30/08/2022
Date registered
1/09/2022
Date last updated
1/09/2022
Date data sharing statement initially provided
1/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet against the innovator 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet conducted under fasting conditions in healthy male and female volunteers
Scientific title
A single dose, randomized, blinded, pharmacokinetic study of a generic formulation of 2.5 mg 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet against the innovator 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet conducted under fasting conditions in healthy volunteers.
Secondary ID [1] 307829 0
None
Universal Trial Number (UTN)
U1111-1281-2570
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate is indicated for the treatment of hypertension. 327435 0
Condition category
Condition code
Cardiovascular 324558 324558 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention for this trial is the test formulation of 1 x 2.5 mg 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet given once only.

Each dose is separated by a one week washout period.

No water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with each dose).

Participants are required not to eat for 10 hours before dosing and to fast for approximately 4 hours after each dose.

Bathroom visits will be supervised to ensure no unauthorized water or food intake and for personal safety.

Participants will be confined at the Clinical Site for 12 hours prior to dosing to ensure compliance and for 24 hours after dosing.

Participants will be monitored for adverse events throughout the study.

Standard meals will be consumed at the Clinical Site with no additional food intake allowed. Alcohol breath testing and urine dipstick drugs of abuse testing will be performed upon each participant reporting to the Clinical Site 12 hours prior to dosing.

Screening and study exit laboratory tests will be completed to assess the health of the participants along with HIV, Hepatitis and drugs of abuse testing.

Each dose will be taken orally with 240 ml of water at ambient temperature. Medication must be swallowed whole and a mouth check will be conducted to ensure that the medication has been taken as directed.
Intervention code [1] 324296 0
Treatment: Drugs
Comparator / control treatment
The comparator/control for this trial is the innovator 1 x 2.5 mg 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet
Control group
Active

Outcomes
Primary outcome [1] 332384 0
To evaluate the pharmacokinetics (as summarised by Cmax and AUC) of the test formulation relative to that of the innovator formulation. All plasma samples will be assayed for 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet using one fully validated LC/MS/MS method. Validation will be conducted to comply with TGA guidelines.
Timepoint [1] 332384 0
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 14, 18, 24, 32, 48, 56 and 72 hours post dosing.
Secondary outcome [1] 413268 0
Time to maximum peak concentration (Tmax) will be determined by plasma sample analysis. Tmax will be the time where the maximum concentration occurred in the sample points.
Timepoint [1] 413268 0
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 14, 18, 24, 32, 48, 56 and 72 hours post dosing.

Eligibility
Key inclusion criteria
Healthy males and females
Aged between 18 and 55 years
Non-smoker
BMI greater than or equal to 18 and less than 32 inclusive
Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests
Drug free as determined by urine drug testing
Able to comply with the study restrictions
Able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Clinically significant medical conditions
History of conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
History of hypertension or hypotension.
History of gingivitis or periodontitis.
History of alcohol or drug abuse or dependency
Participation in a drug study within 30 days of the start of the study
Sensitivities to the study drug or excipients
Individuals for whom the Clinical Investigator believes, for any reason, that participation would not be an acceptable risk

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)
The subject ID will be used to randomise each participant onto the study. Allocation concealment will be completed by the pharmacy staff who are independent of subject recruitment and who are unaware of the identity of each subject.

All staff obtaining consent and confirming eligibility will remain blinded as to what formulation each subject ID has been allocated. Blinding will be broken if the identity of study drug administered to a participant needs to be known.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization by computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
19/09/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment outside Australia
Country [1] 24975 0
New Zealand
State/province [1] 24975 0
Otago

Funding & Sponsors
Funding source category [1] 312103 0
Commercial sector/Industry
Name [1] 312103 0
Arrotex Pharmaceuticals Pty Ltd
Country [1] 312103 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
PO Box 1777
156 Frederick St
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 313623 0
None
Name [1] 313623 0
Address [1] 313623 0
Country [1] 313623 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311506 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 311506 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 311506 0
New Zealand
Date submitted for ethics approval [1] 311506 0
04/08/2022
Approval date [1] 311506 0
25/08/2022
Ethics approval number [1] 311506 0
2022 FULL 13045

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test formulation relative to that of the innovator formulations, following oral administration of a 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate extended release tablet. In this study we will measure how much 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate is absorbed into the bloodstream and compare the concentrations between the test and reference formulations.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121338 0
Dr Noelyn Hung
Address 121338 0
Zenith Technology Corp Ltd
PO Box 1777
156 Frederick St
Dunedin 9054
Country 121338 0
New Zealand
Phone 121338 0
+64 21 482 148
Fax 121338 0
+64 3 477 9605
Email 121338 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 121339 0
Mrs Linda Folland
Address 121339 0
Zenith Technology Corp Ltd
PO Box 1777
156 Frederick St
Dunedin 9054
Country 121339 0
New Zealand
Phone 121339 0
+64 3 477 9669
Fax 121339 0
+64 3 477 9605
Email 121339 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 121340 0
Dr Tak Hung
Address 121340 0
Zenith Technology Corp Ltd
PO Box 1777
156 Frederick St
Dunedin 9054
Country 121340 0
New Zealand
Phone 121340 0
+64 3 477 9669
Fax 121340 0
+64 3 477 9605
Email 121340 0
tak.hung@zenithtechnology.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All data will be compiled into a final report that is the property of the sponsor company


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.