Parkinson's Disease, Parkinsonism Nervous System Diseases
Conditions
Interventions
This is a non-interventional biomarker study. No investigational drug will be administered. Sampling of the biomarkers will be done via blood sampling and CSF sampling. All collections will be perform
Sponsors
Arvinas (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 – 70 years of age at screening (inclusive). 2. BMI in the range of 18 – 30 kg/m², inclusive at screening and with a minimum weight of 50 kg. 3. Able to speak, read, and understand study procedures in Dutch sufficiently to allow completion of all study assessments. 4. Must understand and provide written informed consent prior to the initiation of any protocolspecific procedures. 5. Women of childbearing potential must use an effective form of contraception (e.g., oral contraceptive, condom use, IUD, abstinence of heterosexual intercourse) during the study.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated to confirm eligibility or judged to be clinically irrelevant for healthy participants. 3. Positive serology for human immunodeficiency virus (HIV), hepatitis B virus (HBV) (positive hepatitis B core antibody [anti-HBc] with negative hepatitis B DNA is acceptable), or hepatitis C virus (HCV) (treated/resolved hepatitis C with negative polymerase chain reaction [PCR] RNA is allowed). 4. Vital sign measurements outside the following ranges during screening: - body temperature, >35C to =38C - systolic blood pressure, >90 to =150 mm Hg - diastolic blood pressure, >50 to =90 mm Hg - pulse rate, >45 to =100 bpm 5. Abnormal findings in the resting ECG at screening defined as: - QTcF> 450 or 470 or 100 bpm) - Other abnormal findings in the resting ECG as determined by the investigator 6. Females who have a positive serum or urine pregnancy test. 7. Female participant is pregnant, planning to become pregnant during the study conduct, or is breast feeding. 8. Use of any medications (prescription or over-the-counter [OTC] including herbal medication), within 14 days prior to the first blood collection on day 1, or less than 5 half-lives (whichever is longer), except for birth control, paracetamol (up to 4 g/day), and ibuprofen (up to 1g/day). Other exceptions will only be made if the rationale is clearly documented by the investigator. 9. Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to day 1 of this study, or less than 5 half-lives, whichever is longer). 10. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 14 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent 11. Positive test for drugs of abuse at screening or at day 1. 12. Alcohol will not be allowed from at least 24 hours before screening or day 1. 13. Smoker of more than 10 cigarettes per day prior to screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking whilst in the unit. 14. Is demonstrating excess in caffeine consumption (more than eight cups of coffee or equivalent per day). 15. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable). 16. Loss or donation of blood over 500 mL within 3 months prior to screening or intention to donate blood or blood products during the study. 17. Any known factor, condit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate longitudinal intraindividual and inter-individual variability of whole blood and/or PBMC biomarkers in healthy participants on Day 1: 0h, 4h, 8h. Day 2, 4, 8 and 15: 1. LRRK2 protein (pg/mL) in whole blood and PMBCs 2. Total protein (ug/mL) in PBMCs 3. LRRK2/total protein ratio in PBMCs 4. pS935 LRRK2, total LRRK2 and pS935 LRRK2/total LRRK2 peptide ratio in PBMCs 5. pRab10, Rab10 and pRab10/Rab10 peptide ratio in PBMCs | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate longitudinal intraindividual and inter-individual variability of CSF LRRK2 and correlation of LRRK2 measurement in 3 different assays in healthy participants on Day 1 0h and Day 2 (Day 2 only for subjects in group B = 5) 1. LRRK2 protein (pg/mL) as measured by SISCAPA assay 2. LRRK2 protein (pg/mL) as measured by middomain SIMOA assay 3. LRRK2 protein (pg/mL) as measured by N-terminal SIMOA assay | — |
Countries
Netherlands
Outcome results
None listed