A drug-drug interaction study of BIIB122/DNL151 in healthy volunteers
Research type
Research Study
Full title
A Drug Drug Interaction Study of the Effect of BIIB122/DNL151 on Midazolam Pharmacokinetics in Healthy Participants
IRAS ID
303787
Contact name
G Brill
Contact email
Sponsor organisation
Denali Therapeutics Inc.
Eudract number
2021-002708-10
Duration of Study in the UK
0 years, 1 months, 12 days
Research summary
Research Summary\n\nThe purpose of this study is to investigate the study drug BIIB122/DNL151.\n\nThe objectives of this study are:\n- To determine if there any effects/interactions between BIIB122/DNL151 and midazolam, to determine how BIIB122/DNL151 affects the safety, tolerability (degree to which side effects of \na drug can be tolerated) and amount of midazolam in the blood.\n\n- To determine the safety and tolerability of BIIB122/DNL151 when it is administered once daily alone and when it is administered along with a single dose of midazolam.\n\n- To investigate the amount of a metabolite (products produced when a drug is broken down in the body) of midazolam, 1’hydroxymidazolam in the blood, and to measure how this differs when midazolam is taken on its own versus in combination with BIIB122/DNL151. \n\n- To investigate the amount of midazolam in the blood, and to measure how this differs when midazolam is taken on its’ own versus in combination with BIIB122/DNL151.\n\nThis study is classed as a drug-drug interaction study where participants are given a drug which has known effects and a known method of breakdown (metabolism) in the body (midazolam) and then given the study drug (BIIB122/DNL151) to determine if there is any effect or interaction between the drugs in the body. \n\nIn the study, participants will take a single dose of midazolam (2 milligrams - mg) on Day 1, followed by BIIB122/DNL151 once daily for 9 days (225 mg per dose) up to Day 10 before taking a single dose of both BIIB122/DNL151 and midazolam together on Day 11.\n\nBlood samples will be taken at set time points throughout the study in order to measure the amount of BIIB122/DNL151 and midazolam in the blood and to evaluate how the amount of midazolam differs when it is taken alone versus when it is taken with BIIB122/DNL151.\n\nSummary of Results\n\nThe purpose of this study was to investigate the study drug BIIB122/DNL151 and determine if there were any effects/interactions between BIIB122/DNL151 and midazolam (a drug commonly used before medical procedures and surgery to cause drowsiness and sometimes used in the treatment of anxiety and insomnia). The overall objectives of the study were as follows:\n\n- To investigate the amount of midazolam in the blood, and to measure how this amount differed when midazolam was taken on its own versus in combination with BIIB122/DNL151.\n\n- To investigate the amount of a metabolite (products produced when a drug is broken down in the body) of midazolam, 1’-hydroxymidazolam in the blood, and to measure how this amount differed when midazolam was taken on its own versus in combination with BIIB122/DNL151. \n\n- To investigate the amount of BIIB122/DNL151 in the blood when it is administered in multiple doses.\n\n- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of BIIB122/DNL151 when it was administered once daily alone and when it was administered along with a single dose of midazolam.\n\nThis study was classed as a drug-drug interaction study. This means that participants were administered a drug (midazolam) with known effects and a known method of breakdown (metabolism) in the body and then given the study drug (BIIB122/DNL151) to determine if there was any interaction between the drugs in the body and whether administration of BIIB122/DNL151 affects the safety, tolerability and amount of midazolam in the blood. \n\nThis study involved 14 healthy volunteers and during the study participants were required to take a single dose of midazolam on Day 1, followed by BIIB122/DNL151 once daily for 9 days up to Day 10 before taking a single dose of both BIIB122/DNL151 and midazolam together on Day 11. \n\nParticipants were administered BIIB122/DNL151 in the form of tablets and midazolam was administered in the form of an oral solution. Blood samples were taken at set time points throughout the study in order to measure the amount of BIIB122/DNL151 and midazolam in the blood and to evaluate how the amount of midazolam differed when it was taken alone versus when it was taken with BIIB122/DNL151. \n\nThe purpose of this was to support the study sponsor in developing guidance as to how the BIIB122/DNL151 product should be administered in future clinical studies of the product and how BIIB122/DNL151 may interact with other drugs.\n\nWith respect to the assessment of the drug-drug interactions, BIIB122/DNL151 demonstrated a weak potential for drug-drug interaction for drugs such as midazolam, as the levels of midazolam in the blood showed a slight decrease only in the presence of BIIB122/DNL151.\n\nWith respect to the safety objectives of the study, it was determined that BIIB122/DNL151 was considered to be safe and well tolerated, both in the presence and absence of midazolam. All adverse events (side effects) which were reported were considered to be mild to moderate in severity and resolved before the study completed, either without any treatment or treatment with some medications to manage the symptoms.\n\nIn summary, the data gathered during the study was considered sufficient to meet the objectives of the study and results support further development of BIIB122/DNL151 for the treatment of Parkinson’s disease.
REC name
Wales REC 1
REC reference
21/WA/0261
Date of REC Opinion
13 Sep 2021
REC opinion
Favourable Opinion