Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000019505p
Ethics application status
Not yet submitted
Date submitted
6/12/2023
Date registered
11/01/2024
Date last updated
11/01/2024
Date data sharing statement initially provided
11/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Bioequivalence study of loratadine 5mg Chewable Tablets of AFT Pharmaceuticals compared with Children's Claratyne® Grape 5mg Chewable Tablets in healthy human adults under fasting conditions.
Scientific title
A Randomized, Open Label, Balanced, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Two-Way Crossover, Bioequivalence Study of Loratadine 5mg Chewable Tablets of AFT Pharmaceuticals, Australia Compared with Children's Claratyne® Grape 5 mg Chewable Tablets in Healthy Human Adult Subjects Under Fasting Conditions.
Secondary ID [1] 311095 0
GR-23-038
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergies 332250 0
Condition category
Condition code
Inflammatory and Immune System 328968 328968 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will be randomly allocated to receive a single dose of each of the Test product (T), and the Reference product (R) under fasting conditions in a two-way crossover sequence:

Test product (T): Loratadine 5mg Chewable Tablets manufacture for AFT Pharmaceuticals, Australia

Administration: Following an overnight fast of at least 10 hours, subjects will be dosed one tablet at ambient temperature in an upright sitting position as per the randomization schedule. Subjects will be housed in Genecht's Clinical Pharmacology Unit where dosing and administration will take place.

The dosing and administration process as detailed below will be conducted by either the Principal Investigator or a research personnel designated by the Principal Investigator:
•Subject will wet their mouth with 20 ± 2 ml of water by swallowing, just 20 seconds before dosing.
•Subject will chew the tablet slowly and thoroughly.
•Mouth check will be performed immediately after the subject indicated that the tablet was completely chewed
•Once this is confirmed, the subject will be instructed to swallow the chewed tablet mass.
•All the subjects shall be instructed not to spit the saliva and phlegm until one hour after dosing.
•Subjects will be instructed to remain in upright posture for at least 04.00 hours post-dose except for essential reasons (e.g., use of washroom) or study procedures.

Compliance for dosing will be assessed by a thorough check of the oral cavity with a torch and disposable tongue depressor immediately after dosing.

There will be two study periods separated by a washout period of at least 14 days will be maintained between each dosing period. Subjects will be checked out after 24 hours post-dose during each study period.
Intervention code [1] 327546 0
Treatment: Drugs
Comparator / control treatment
The comparator treatment is described below:

Reference product (R): Children's Claratyne® Grape 5 mg Chewable Tablets manufactured for Bayer Australia Ltd

Administration: Following an overnight fast of at least 10 hours, subjects will be dosed one tablet at ambient temperature in an upright sitting position as per the randomization schedule.
•Subject will wet their mouth with 20 ± 2 ml of water by swallowing, just 20 seconds before dosing.
•Subject will chew the tablet slowly and thoroughly.
•Mouth check will be performed immediately after the subject indicated that the tablet was completely chewed
•Once this is confirmed, the subject will be instructed to swallow the chewed tablet mass.
•All the subjects shall be instructed not to spit the saliva and phlegm until one hour after dosing.
•Subjects will be instructed to remain in upright posture for at least 04.00 hours post-dose except for essential reasons (e.g., use of washroom) or study procedures.

Compliance for dosing will be assessed by a thorough check of the oral cavity with a torch and disposable tongue depressor immediately after dosing.

There will be two study periods separated by a washout period of at least 14 days will be maintained between each dosing period. Subjects will be checked out after 24 hours post-dose during each study period.
Control group
Active

Outcomes
Primary outcome [1] 336770 0
To compare the rate of absorption of Loratadine 5mg Chewable Tablets of AFT Pharmaceuticals, Australia with Children's Claratyne® Grape 5 mg Chewable Tablets of Bayer Australia Ltd. in normal, healthy, adult human subjects under fasting conditions.
Timepoint [1] 336770 0
Blood samples will be collected at 00.00 (within 02.00 hours prior to dosing), 00.33, 00.67, 01.00, 01.33, 01.67, 02.00, 02.25, 02.50, 02.75, 03.00, 03.33, 03.67, 04.00, 05.00, 06.00, 08.00, 10.00, 12.00, 24.00, 48.00, 72.00- and 96.00-hours post-dose in a pre-labelled vacutainers containing K2EDTA as an anticoagulant during each study period.

Blood samples will be collected within +2 minutes of scheduled sampling time and kept in a wet ice bath. Any delay in sample collection from the scheduled sampling time will be reported as PK sampling deviations as per in-house SOP.
Primary outcome [2] 336906 0
To compare the extent of absorption of Loratadine 5mg Chewable Tablets of AFT Pharmaceuticals, Australia with Children's Claratyne® Grape 5 mg Chewable Tablets of Bayer Australia Ltd. in normal, healthy, adult human subjects under fasting conditions.
Timepoint [2] 336906 0
Blood samples will be collected at 00.00 (within 02.00 hours prior to dosing), 00.33, 00.67, 01.00, 01.33, 01.67, 02.00, 02.25, 02.50, 02.75, 03.00, 03.33, 03.67, 04.00, 05.00, 06.00, 08.00, 10.00, 12.00, 24.00, 48.00, 72.00- and 96.00-hours post-dose in a pre-labelled vacutainers containing K2EDTA as an anticoagulant during each study period.

Blood samples will be collected within +2 minutes of scheduled sampling time and kept in a wet ice bath. Any delay in sample collection from the scheduled sampling time will be reported as PK sampling deviations as per in-house SOP.
Secondary outcome [1] 429638 0
To monitor the safety and tolerability of single oral dose of Loratadine 5mg Chewable Tablets in normal, healthy, adult human subjects under fasting conditions. The safety and tolerability will be assessed as a composite secondary outcome.
Timepoint [1] 429638 0
Subjects will be housed in Clinical Pharmacology Unit (CPU) from at least 10.00 hours prior to dosing and confined until 24.00 hours post-dose during each study period.
Vital signs measurements (blood pressure, radial pulse, body temperature and respiratory rate) and general well-being will be assessed within 02.00 hours prior to dosing; and blood pressure, radial pulse, body temperature and general well-being will be assessed at 01.00, 03.00, 05.00 and 11.00 post-dose (±01.00 hour of scheduled time) during the in-house stay of subjects.

Medical examination, vital signs measurements (blood pressure, radial pulse, body temperature and respiratory rate) and well-being will be evaluated at check-out (up to -02.00 hours from scheduled time) during each study period, and during the occurrence of any AE or termination/withdrawal of subject from the study.

Post-study safety evaluations will be done after 96.00 hours post-dose of period II (up to -02.00 hours from scheduled time except blood sample collection for post-study safety evaluation) or at the time of withdrawal/termination of the subject.

Subjects will be instructed to inform the investigator or clinic staff regarding occurrence of any AE during the washout period until completion of clinical phase. Subjects will be asked to report to the clinic for further safety follow-up. Apart from scheduled safety monitoring times, the Principal Investigator/designee can monitor the health of subjects at any time during the study, if required. Subjects will be followed up for any AE until resolution., except in case of lost to follow up.

Eligibility
Key inclusion criteria
A subject fulfilling all of the following criteria will be included in the study:
•Willing to provide written informed consent to participate in the study, and an ability to comprehend the nature and purpose of the study;
•Subjects with healthy oral cavity.
•Willing to be available for the entire study duration and to comply protocol requirements;
•Normal, healthy, adult human subject of 18 to 45 years (both inclusive) of age and weight greater than or equal to 50 Kg;
•Body mass index in the range of 18.50 to 30.00 kg/m2 (both inclusive);
•Normal health status as determined by baseline medical and medication history, at the time of screening and vital signs measurements and medical examination at the time of screening as well as check-in of each study period;
•Normal or clinically non-significant laboratory values as determined by haematological, biochemistry tests and urine analysis;
•Normal or clinically non-significant 12-lead ECG recording;
•Non-smokers or mild/moderate smokers with not more than 10 bidis/cigarettes/pipes per day;
•Willing to abstain from alcohol or alcoholic products at least 24.00 hours prior to dosing until last sample collection in each study period;
•Willing to abstain from grapefruit or its juice at least 72.00 hours prior to dosing until last sample collection in each study period;
•Willing to abstain from smoking or chewing any tobacco containing product and xanthine or its derivative containing food or beverages (e.g., chocolates, tea, coffee or cola drinks), at least 48.00 hours prior to dosing until last sample collection in each study period;
•For female subjects:
-Negative urine pregnancy test during screening and negative serum ß-hCG test at the time check-in of each study period;
-Female subjects with child bearing potential or those within their first two years of onset of menopausal syndrome willing to either abstain from sexual intercourse, or use of acceptable birth control methods for at least 15 days before 1st dosing till 15 days post last-dose [Acceptable birth control methods include barrier methods such as diaphragm/condom with or without spermicide or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed)].
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A subject meeting any one of the following criteria will be excluded from the study:
•Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract and of blood forming organs;
•Significant history or current evidence of malignancy or chronic - infectious, cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic (endocrine), haematological, gastrointestinal, dermatological, immunological or psychiatric diseases, or organ dysfunction;
•Any major illness or hospitalized within 90 days prior to the first dosing;
•Requiring medication for any ailment having enzyme-modifying activity within one month prior to first dosing until last blood sample collection in the study;
•Use of any depot injection or an implant of any drug within 03 months prior to first dosing until last blood sample collection in the study;
•Use of any prescribed medication or OTC products (including herbal medicines and vitamin supplements) within 30 days prior to dosing of period I and throughout the study;
•Subject who can’t hold the saliva in mouth for 01.00 hour.
•Difficulty in chewing and swallowing IMPs
•Subjects which having teeth disorders i.e., periodontitis, tooth decay, gingivitis, teeth arrangement, dry mouth, mouth ulcer etc.
•History or presence of significant gastric and/or duodenal ulceration;
•Use of any recreational drug or history of drug addiction;
•Participated in any clinical investigation requiring repeated blood sampling or have donated blood in past 90 days prior to first dosing;
•Positive breath alcohol and urine drugs of abuse tests during check-in of each study period;
•Positive test for Human Immunodeficiency Virus (HIV) type I/II antibodies or Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibodies;
•Pregnant or lactating or nursing female subjects;
•Female subjects using hormonal contraceptive (either oral/implants);
•History of allergy or hypersensitivity intolerance to Loratadine and Desloratadine or related group of drugs or its formulation excipients which, in the opinion of a Principal Investigator, would compromise the safety of the subject or the study;
•History of difficulty in accessibility of veins in arms.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Biostatistician will generate a randomization schedule for all study periods prior to dispensing in period I by PROC SEED procedure (such that the design is balanced over the period and sequence combination) using Statistical Analysis Software SAS® (SAS Institute Inc., USA) Version 9.4 or higher.
Study subjects will be allocated sequential numbers starting from 01. On the day of dosing, subjects will be administered either test product (T) or reference product (R) on separate occasions in each study period as per the randomization schedule.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis
Statistical analysis will be performed using SAS® (SAS Institute Inc., USA) Version 9.4 or higher.
The observed plasma concentrations will be tabulated for each subject – product combination. Descriptive statistics including number of observations, arithmetic mean, standard deviation, range (minimum – maximum), median and coefficient of variation for untransformed data of all PK parameters, and geometric least square means and Intra CV (%) for Ln-transformed data (primary PK parameters) for test and reference products.
Concentration and PK parameters data from dropouts, withdrawn and terminated subjects will be presented in the individual listings, but will not be included in the summary statistics.
The mean and individual subject’s plasma concentrations, for Loratadine and Desloratadine versus time profiles for each product will be presented graphically as linear and semi-log plots, respectively.
The ratio of untransformed data of test and reference product for primary PK parameters will also be reported. PROC GLM will be used for the estimation of LSM differences of test and reference products on the Ln-transformed primary PK parameters for Loratadine and Desloratadine along with the computation of corresponding standard errors. The 90% CIs will be constructed for the LSM differences of Ln-transformed primary PK parameters. The antilog (or exponential) of the limits obtained from the Ln-transformed data will give the 90% CI for the ratio of geometric least square means of test and reference products.
The statistical analysis will include:
a) Two one-sided ANOVA test;
b) Ratio analysis;
c) Power analysis and
d) Acceptance criteria for bioequivalence.
Consistent with Schuirmann’s two one-sided tests procedure for bioequivalence, ANOVA at 5% level of significance will be performed on Ln-transformed PK parameters Cmax and AUC0-t to determine whether the average values for these PK measures determined after administration of the test and reference products are comparable. This will involve the calculation of 90% CI for the ratio of the averages (population geometric least square means) of the measures for test and reference products. The ANOVA model will include sequence, subjects nested within sequence, period and treatment as fixed effects factors. The significance of the sequence effect will be tested using the subjects nested within sequence as the error term. Each ANOVA testing will also include calculation of LSM, adjusted differences between formulation means and the standard error associated with these differences.
Non-parametric analysis of Tmax will be performed on untransformed data, using the Wilcoxon signed-rank test.
Geometric least square mean values will be reported for Ln-transformed primary PK parameters of Loratadine and Desloratadine on which CI is based. Ratios of means are expressed as a percentage of the LSM for the test and reference products.
The test product will be considered bioequivalent to the reference product, if 90% confidence intervals for ratio (test/reference) of geometric least square means based on Ln-transformed primary PK parameters - Cmax and AUC0-t fall within acceptable BE limits of 80.00% to 125.00% for Loratadine and Desloratadine.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/04/2024
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] 26020 0
India
State/province [1] 26020 0
Maharashtra

Funding & Sponsors
Funding source category [1] 315354 0
Commercial sector/Industry
Name [1] 315354 0
AFT Pharmaceuticals Ltd
Country [1] 315354 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
AFT Pharmaceuticals Ltd
Address
Level 1, 129 Hurstmere Road, Takapuna, Auckland 0622, New Zealand
Country
New Zealand
Secondary sponsor category [1] 317414 0
None
Name [1] 317414 0
Address [1] 317414 0
Country [1] 317414 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 314273 0
Humancare Independent Ethics Committee
Ethics committee address [1] 314273 0
Shop no 16, Lodha Elite, near Nilje Railway station lodha heaven, dombivali (east) thane 421204, India
Ethics committee country [1] 314273 0
India
Date submitted for ethics approval [1] 314273 0
14/03/2024
Approval date [1] 314273 0
Ethics approval number [1] 314273 0
Ethics committee name [2] 314284 0
Ethos Ethics Committee
Ethics committee address [2] 314284 0
2, Ashiv Apartment, Sector 5, Opp Kopar khairne Railway station, Kopar Khairne, Navi Mumbai 400709 Maharashtra, India
Ethics committee country [2] 314284 0
India
Date submitted for ethics approval [2] 314284 0
14/03/2024
Approval date [2] 314284 0
Ethics approval number [2] 314284 0

Summary
Brief summary
This study is designed as a bioequivalence study to compare the rate and extent of absorption of Loratadine 5mg Chewable Tablets of AFT Pharmaceuticals, Australia with Children's Claratyne® Grape 5 mg Chewable Tablets of Bayer Australia Ltd. in normal, healthy, adult human subjects. This study will include 32 healthy volunteers and will be conducted under fasting conditions. The study aims to demonstrate that Loratadine 5mg Chewable Tablets of AFT Pharmaceuticals, Australia is absorbed and cleared from the body in the same way and has a similar safety profile to Children's Claratyne® Grape 5 mg Chewable Tablets of Bayer Australia Ltd. It is hypothesized that both products will have similar absorption, clearance, and safety profiles.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131014 0
Dr Spenta Katrak
Address 131014 0
Contract Research Organization Genecht Research Pvt. Ltd. Plot No. D-400, TTC Industrial Area, MIDC Nerul, Uran Phata Junction, Off Sion - Panvel Expy, Nerul, Navi Mumbai-400 706, Maharashtra, India.
Country 131014 0
India
Phone 131014 0
+919987154253
Fax 131014 0
Email 131014 0
[email protected]
Contact person for public queries
Name 131015 0
Dr Laura Boddington
Address 131015 0
AFT Pharmaceuticals Ltd. Level 1, 129 Hurstmere Road, Takapuna, Auckland, New Zealand 0622
Country 131015 0
New Zealand
Phone 131015 0
+64 9 4880232
Fax 131015 0
Email 131015 0
[email protected]
Contact person for scientific queries
Name 131016 0
Dr Laura Boddington
Address 131016 0
AFT Pharmaceuticals Ltd. Level 1, 129 Hurstmere Road, Takapuna, Auckland, New Zealand 0622
Country 131016 0
New Zealand
Phone 131016 0
+64 9 4880232
Fax 131016 0
Email 131016 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


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.