A BA/BE study of KL-00119 in healthy volunteers
Research type
Research Study
Full title
A Phase 1, 2-part randomised crossover study to investigate the safety, tolerability, PK and comparative bioavailability of KL-00119 in comparison with Imitrex & Imigran including assessment of accidental swallowing and food effect.
IRAS ID
284853
Contact name
Ezanul Wahab
Contact email
Sponsor organisation
Klaria AB
Eudract number
2020-003518-11
Duration of Study in the UK
0 years, 2 months, 18 days
Research summary
Summary of Research
The purpose of this study is to investigate KL-00119 (active ingredient sumatriptan). Sumatriptan is a drug which is used in the treatment of migraines.
This study will evaluate the bioequivalence (assessment of whether products can be considered the same in terms of effect) and bioavailability (the degree and rate at which a substance (such as a drug) is absorbed into the body or is made available at the site of its’ desired effect) of KL-00119 compared with marketed migraine products (Imitrex and Imigran). The study will evaluate the effect of accidental swallowing of the KL-00119 product following an overnight fast and a high fat breakfast on the levels of sumatriptan in the blood.Sumatriptan will be given in 2 forms; KL-00119 the test drug is an oral film designed to stick to the lining of the cheek and Imitrex and Imigran are marketed nasal sprays which deliver the drug in a form of aerosol spray into the nose.
The study will be split into 2 parts; Part A and Part B.
In Part A, participants will take a single dose of each of the products (KL-00119, Imitrex and Imigran) across 3 treatment periods.
In Part B, participants will take a single dose of KL-00119 across two treatment periods; once after an overnight fast and once after consumption of a high fat breakfast. In this part of the study, participants will be asked to swallow the KL-00119 product instead of sticking it to the lining of their cheek.
Blood samples will be taken to measure the levels of sumatriptan in the blood to determine whether there are any differences between the 3 products and to determine if food and accidental swallowing of the product has any effect.
The study will enrol 68 participants; 60 in Part A, 8 in Part B.
Summary of Results
The purpose of this study was to investigate the study drug KL-00119 (active ingredient sumatriptan) which is used in the management and treatment of migraines in adults with or without aura.The objectives of this study were to evaluate and compare the bioequivalence (assessment of whether products can be considered the same in terms of effect) and bioavailability (the degree and rate at which a substance (such as a drug) is absorbed into the body or is made available at the site of its’ desired effect) of KL-00119 as an oral mucosal film in comparison with marketed reference products (Imitrex and Imigran nasal sprays).
The study also evaluated the effect of accidental swallowing of the KL-00119 product following an overnight fast and following consumption of a high fat breakfast and how this impacted on the levels of sumatriptan in the blood in addition to providing general safety information for all 3 products.
In the study, sumatriptan was administered in 2 different forms. KL-00119 the test study drug was administered as an adhesive oral film which is designed to stick to the lining of the cheek and allows the drug to be delivered directly into the bloodstream. Imitrex and Imigran the study reference products (which are already marketed sumatriptan products in the USA and UK respectively) were administered in the form of a nasal spray which delivers the drug in a form of an aerosol spray into the nose where it is absorbed into the bloodstream.
The study was split into 2 parts; Part A and Part B. In Part A, participants were given a single dose of each of the products (KL-00119, Imitrex and Imigran) across 3 treatment periods and blood samples taken as set time points in each period to measure the levels of sumatriptan in the blood and how this changed over time and differed between the 3 products.
In Part B, participants were given a single dose of KL-00119 across two treatment periods; once after an overnight fast and once after consumption of a high fat breakfast. In this part of the study, participants were asked to swallow the KL-00119 product instead of sticking it to the lining of their cheek. Blood samples were taken as set time points in each period to measure the levels of sumatriptan in the blood and to determine if food and accidental swallowing of the product had any effect on these levels.
The purpose of the data generated in this study was to determine whether the KL-00119 oral film product is equivalent and as effective or more/less effective than currently marketed products for treatment of migraine and 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 KL-00119 was considered to be safe and well tolerated at a 27 mg dose strength, with reported side effects for this product aligning with similar side effects observed for the marketed reference products (Imitrex and Imigran nasal sprays). In addition, the assessment of the safety of the KL-00119 product in the mouth showed that the product did not cause any discomfort or irritation in the mouth and was considered acceptable from a taste perspective. All adverse events (side effects) which were reported were considered to be mild to moderate in severity and resolved shortly after administration of the products.
With respect to the assessment of the bioequivalence of KL-00119 and the effect of accidental swallowing, the following outcomes were reported:
• It was determined that the 27 mg KL-00119 product is considered as a bioequivalent product to the marketed reference products (20 mg Imitrex and Imigran nasal sprays) as the levels of the sumatriptan in the blood compared between the 3 products were measured as being suitably equivalent.
• It is possible that the consumption of food with KL-00119 (or the accidental swallowing of the product) may have some effect on the levels of sumatriptan in the blood. However, it is difficult to determine as to whether this effect is significant or a true effect as this phenomenon was only observed in small number of participants.
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 study drugs.
REC name
Wales REC 1
REC reference
20/WA/0207
Date of REC Opinion
4 Sep 2020
REC opinion
Further Information Favourable Opinion