A BE study to compare 2 formulations of Siklos in healthy volunteers
Research type
Research Study
Full title
A bioequivalence study to compare the pharmacokinetics of two formulations of Siklos® in healthy volunteers.
IRAS ID
300499
Contact name
Annelize Koch
Contact email
Sponsor organisation
Addmedica SAS
Eudract number
2021-002786-18
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 1 months, 22 days
Research summary
Research Summary
The purpose of this study is to investigate the study drug hydroxycarbamide oral dispersible tablets (active ingredient hydroxycarbamide).
The objectives of this study are:
- To investigate the concentration of hydroxycarbamide oral dispersible tablets (test product) in the blood, how this concentration changes over a period of time and to evaluate whether there are differences in the concentration of hydroxycarbamide in the blood between the hydroxycarbamide oral dispersible tablets (test product) and the hydroxycarbamide Siklos® oral film-coated tablet (reference product).- To evaluate the bioequivalence (assessment of whether products can be considered the same in terms of effect) of hydroxycarbamide as an oral dispersible tablet (test product) in comparison with the hydroxycarbamide Siklos® oral film-coated tablet (reference product).
- To determine the safety and tolerability (extent to which side effects of a drug can be tolerated) of hydroxycarbamide oral dispersible tablets (test product) in comparison with a hydroxycarbamide Siklos® oral film-coated tablet (reference product) when they are administered as a single dose of 1000 milligrams (mg).
The study will consist of 3 groups of 10 participants: participants in each group will receive the test and the reference product across 2 treatment periods at the same dose strength (1000 mg). In this study, participants will be given hydroxycarbamide in 2 different forms: the test product as an oral dispersible tablet (to be dissolved in water) and the reference product (Siklos®) as an oral film-coated tablet (to be swallowed with water).
Blood samples will be taken in order to measure the concentration of hydroxycarbamide in the blood. We will compare the results between the test and reference product to determine if there are any significant differences in the safety of hydroxycarbamide, the concentration of hydroxycarbamide, how this changes over time and whether the way in which the hydroxycarbamide is given has any impact on these factors.Summary of Results
The purpose of this study was to investigate the active product hydroxycarbamide which is a marketed product used for the treatment and prevention of symptoms associated with sickle-cell disease.
The main objectives of this study were as follows:
• To investigate the concentration of hydroxycarbamide oral dispersible tablets (test product) in the blood, how this concentration changed over a period of time and to evaluate whether there were differences in the concentration of hydroxycarbamide in the blood between the hydroxycarbamide oral dispersible tablets (test product) and the hydroxycarbamide Siklos® oral film-coated tablet (reference product).
• To evaluate the bioequivalence (assessment of whether products can be considered the same in terms of effect) of hydroxycarbamide as an oral dispersible tablet (test product) in comparison with the hydroxycarbamide Siklos® oral film-coated tablet (reference product).
• To determine the safety and tolerability (extent to which side effects of a drug can be tolerated) of hydroxycarbamide oral dispersible tablets (test product) in comparison with a hydroxycarbamide Siklos® oral film-coated tablet (reference product) when administered as a single dose of 1000 milligrams (mg).
The intention of this study was to demonstrate bioequivalence such that the hydroxycarbamide oral dispersible tablet formulation may proceed into marketing authorisation applications as an alternative dosage form to currently available hydroxycarbamide formulations. The alternative dosage form is intended to be utilised for dosing in paediatric populations or in individuals who have difficulties in swallowing.
This study was conducted in 28 healthy volunteers (males and females of childbearing and non-childbearing potential) and consisted of 1 screening visit, 2 treatment periods (approximately 3 days in duration per period) and a follow up visit 1 to 3 days after the last dose of hydroxycarbamide in treatment period 2. Each treatment period was separated by a washout period of at least 72 hours and at each treatment period, participants were required to take one of the products (either hydroxycarbamide oral dispersible tablets or hydroxycarbamide Siklos® oral film-coated tablet, 1 product per period) in a fasted state.
During the study, blood samples were taken at set timepoints to evaluate the concentration of hydroxycarbamide in the blood for all products, how this concentration changed over time and to determine whether there were significant differences in the profile between each product in order to determine bioequivalence. The purpose of the data generated in this study was to provide further information and guidance to support the study sponsor in development of the study drug.
With respect to the safety objectives of the study, it was determined that both forms of the hydroxycarbamide product were considered to be safe and well tolerated at a 1000 mg dose strength. All adverse events (side effects) which were reported were considered to be mild to moderate in severity and resolved before the study completed. Further to this, the reported side effects were similar between both products and were aligned to the reported side effects for marketed hydroxycarbamide products.
With respect to the assessment of the bioequivalence of the hydroxycarbamide test product and Siklos®, the following outcomes were reported:
• The comparison of the concentration of hydroxycarbamide in the blood and the way in which the concentration profile of hydroxycarbamide changed over time between the two products showed that these profiles were very similar in nature.
• Based on these criteria, it was determined that the test product hydroxycarbamide oral dispersible tablets (test product) and the hydroxycarbamide Siklos® oral film-coated tablet (reference product) were considered to be bioequivalent.
In summary, the data gathered during the study was considered sufficient to meet the objectives of the study and warrant further clinical trials and investigations of the test product.
REC name
Wales REC 2
REC reference
21/WA/0182
Date of REC Opinion
10 Jun 2021
REC opinion
Favourable Opinion