A study to evaluate the PK and PD of DNL201 in healthy volunteers
Research type
Research Study
Full title
A Phase 1, Single-Center, Randomized, Placebo-Controlled, Double-Blind, Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of DNL201 SR MUPS Capsules in Healthy Subjects
IRAS ID
285250
Contact name
Annelize Koch
Contact email
Sponsor organisation
Denali Therapeutics Inc.
Eudract number
2020-002490-98
Duration of Study in the UK
0 years, 1 months, 26 days
Research summary
Research Summary\n\nThe purpose of this study is to investigate the study drug DNL201.\n\nThe main purposes of this study are as follows:\n•To measure how the levels of DNL201 change in the blood over the study period (known as pharmacokinetics or what the body does to the drug).\n•To investigate the effect of DNL201 on the body (known as pharmacodynamics or what the drug does to the body).\n•To investigate the safety of DNL201 when it is given as multiple doses (twice per day) over a period of 10 days.\n\nIn this study, the above factors will be evaluated when the study drug (DNL201) is given twice a day over a period of 10 days in the form of a sustained release, multiple unit pellet system (SR MUPS) capsule. This type of capsule allows for the study drug to be released in small quantities (using a pellet) into the blood over a longer period than a standard immediate release capsule (where all the drug is released at once).\n\nThe study drug (DNL201) will be given at 2 different dosage strengths; 60 milligrams (mg) and 120 mg with a matching placebo for both doses. In this study, participants will be allocated to one of the dose strengths (10 participants on 60 mg, 10 participants on 120 mg and 6 participants on a matching placebo).\n\nParticipants will be required to take the capsules twice a day for a period of 10 days (19 doses, morning of Day 1 to morning of Day 10). Blood and urine samples will be taken at set time points throughout the study to measure the objectives described above.\n\nThe study sponsor is developing this drug for the treatment of Parkinson’s Disease which is a long-term progressive disorder of the nervous system.\n\nThe study will be conducted in 26 healthy volunteers (males and females of non-child bearing potential).\n\nSummary of Results\n\nThe purpose of this study was to investigate the study drug DNL201.\n\nThe main objectives of this study were as follows:\n\n• To measure how the levels of DNL201 changed in the blood over the study period (known as pharmacokinetics or what the body does to the drug).\n\n• To investigate the effect of DNL201 on the body (known as pharmacodynamics or what the drug does to the body).\n\n• To investigate the safety of DNL201 when it was given as multiple doses (twice per day) over a period of 10 days.\n\nDNL201 was given at 2 different dosage strengths. The results from each of these dose strengths were compared to determine if there are any significant differences between the two different dose strengths. \n\nThe information from this study will help to support the study sponsor in further development of DNL201 including decisions related to future study designs for DNL201 in Parkinson’s Disease patients.\n\nWith respect to the safety objectives of the study, DNL201 was considered to be safe and well tolerated at both dose strengths, with reported side effects for this product aligning with similar side effects observed during previous clinical trials with DNL201. All adverse events (side effects) which were reported were considered to be mild to moderate in severity and resolved shortly after drug administration.\n\nWith respect to the assessment of the pharmacokinetics and pharmacodynamics of DNL201, the following outcomes were reported: \n\nAccumulation of DNL201in blood was greater in the DNL201 high dose group than in the lower dose group. The variability in DNL201 exposure on Day 10 was low to moderate for both doses. Predose DNL201 concentrations measured prior to the morning dose of DNL201 suggest that steady state was obtained by Day 5.\n\nA decrease in indicators for DNL201 activity (biomarkers) in blood and urine were seen with DNL201 treatment compared with placebo treatment, showing that the drug had inhibited LRRK2 and the LRRK2 pathway.\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 DNL201.
REC name
Wales REC 2
REC reference
20/WA/0173
Date of REC Opinion
29 Jul 2020
REC opinion
Further Information Favourable Opinion