A 2-part PK study of Naloxone formulations in healthy volunteers
Research type
Research Study
Full title
A single-centre, two part, open-label, randomised, cross-over, pharmacokinetic study, to assess naloxone plasma concentrations in healthy volunteers after administration of different forms of Naloxone.
IRAS ID
301902
Contact name
Gabrielle Brill
Contact email
Sponsor organisation
Klaria AB
Eudract number
2021-003911-24
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research\nThe purpose of this study is to investigate the study drug naloxone.\n\nThe objectives of this study are as follows:\n\n- To determine the safety of naloxone when it is administered as single doses in different formulations i.e., as an oral mucosal film (a film which sticks to the inside of the cheek), a nasal spray, and as an intravenous infusion (administering the drug directly into a vein and administering over a period of time).\n\n- To investigate the concentration of naloxone in the blood in order to evaluate whether there are differences in the concentration in the blood between different formulations of naloxone. \n\n- To 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 naloxone in 3 different formulations.\n\nThis study will be split into 2 parts: Parts A & B.\nPart A will investigate naloxone when it is given as single doses in 3 different forms and Part B will investigate naloxone when it is given as single doses in 2 different forms. Part A will enrol 2 groups of 6 participants and Part B will enrol 5 groups of 12 participants.\n\nBlood samples will be taken at set time points throughout this part of the study in order to measure the concentration of naloxone in the blood. The results from each group will be compared to determine if there are any differences in the safety of naloxone, the concentration of naloxone in the blood, how this changes over time and whether the test product KL-00514 can be considered as equivalent to current marketed naloxone products.\n\nSummary of Results\nThe purpose of this study was to investigate the study drug KL-00514.\n\nThe main objectives of this study were as follows:\n\n- To determine the safety and tolerability of naloxone when it is administered as single doses in different formulations i.e., as an oral mucosal film, a nasal spray, and as an intravenous infusion.\n\n- To investigate the pharmacokinetic (PK) profile of naloxone in the blood, how this changed over a period of time and to evaluate whether there were differences in the PK profile in the blood between the different formulations of naloxone.\n\n- To evaluate and compare the bioequivalence and bioavailability of naloxone as an oral mucosal film in comparison with marketed reference products (naloxone nasal spray and naloxone solution for intravenous (IV) infusion).\n\nThe intention of the study was to demonstrate bioequivalence of the naloxone oral mucosal film formulation with marketed comparators, so KL-00514 may proceed into marketing authorisation applications as an alternative dosage form to currently available naloxone formulations.\n\nThe study was split into 2 parts: Part A & Part B. The study intended to enrol 72 healthy males and females (of childbearing or non-childbearing potential); a total of 12 in Part A, and a total of 60 in Part B. However, following analysis of the data from Part A, the decision was made not to proceed with Part B as the analysis confirmed that the test product (KL-00514) did not show sufficient evidence of being comparable to the marketed nasal spray and therefore, further evaluation within Part B was not warranted.\n\nWith respect to the safety objectives of the study, it was determined that the KL-00514 was safe and well tolerated at all dose levels evaluated (3 mg KL-00514 oral mucosal film (OMF) with or without sodium bicarbonate mouth rinse solution).\n\nAll side effects reported were classified as mild or moderate in nature, with most being of reasonable possible relationship to the study drug and resolved following administration of the drug. The effects reported were considered to be in line with the known side effects of naloxone. In addition, there were no other clinically significant changes in any of the other safety parameters evaluated i.e., vital signs, ECGs or laboratory safety testing.\n\nWith respect to the other objectives of the study, (namely related to the levels of the study drug in the blood), the following outcomes were reported:\n\n- The 3mg KL-00514 Oral Mucosal Film (OMF) was not considered bioequivalent to the 4 mg NARCAN® nasal spray.\n\n- The time for 3 mg KL-00514 OMF to reach the maximum concentration was significantly longer when compared to the 4mg NARCAN® nasal spray.\n\n- The naloxone bioavailability was approximately 10% lower following administration of 3 mg KL-00514 OMF alone when compared to administration with sodium bicarbonate solution mouth rinse.\n\n- Mouth-rinsing with sodium bicarbonate solution had no significant effect on the time taken to reach the maximum concentration of naloxone in the blood.\n\n- The study drug (3 mg KL-00514 Oral Mucosal Film) was well tolerated locally, with an acceptable taste.\n\nIn 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 drug.
REC name
Wales REC 1
REC reference
21/WA/0260
Date of REC Opinion
13 Sep 2021
REC opinion
Favourable Opinion