Dementia Mental and Behavioural Disorders Dementia
Conditions
Interventions
Participants are asked to attend four study visits in which each participant receives four treatments (one at each of the study visits). The order in which they receive each dose is randomly allocated
Sponsors
Takeda Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements 2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures 3. Healthy adult as judged by Medical Supervisor 4. Aged 60 to 80 years, inclusive, at the time of informed consent 5. Memory performance between 1 to 2 SD below (for Impaired Elderly) and between 0.5 SD below and 0.5 SD above (for Healthy Elderly) age, gender, and education level corrected normative values assessed using the VLT 6. The subject has normal hearing demonstrated by average audiometric hearing thresholds of 20 dB hearing level (HL) and relatively symmetric hearing (left/right ear asymmetry of 15 dB) 7. Body mass index (BMI) between 18 and 30 kg/m2 inclusive at Screening 8. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose 9. A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to use acceptable methods of contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose 10. Clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) within the reference range for the testing laboratory, unless the results are deemed not to be clinically significant (CS) by the investigator or sponsor at screening and Day 1 of Period 1
Exclusion criteria
Exclusion criteria: 1. Received any investigational compound within 30 days prior to the first dose of study medication 2. Received roflumilast in a previous clinical study or as a therapeutic agent 3. Immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress 4. Uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the subject to participate or potentially confound the study results 5. Previous or existing major psychiatric symptoms (evaluated through semi- Structured Clinical Interview for DSM MINI for the assessment of lifetime DSM-IV Axis -II diagnoses) 6. Known hypersensitivity to any component of the formulation of roflumilast or related compounds 7. Positive urine drug result for drugs of abuse at Screening Visit 2 8. History of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol from 72 hrs prior to Day 1 through Day 2 of each Period and/or drugs throughout the study 9. Taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table listed in Section 7.3 10. Evidence of uncontrolled cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the subject’s medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking roflumilast or a similar drug in the same class, or that might interfere with the conduct of the study as judged by Medical Supervisor. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias. 11. Current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [eg, cholecystectomy, bariatric surgery]) 12. History of cancer within the past 5 years prior to the first dose of study medication. This criterion does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin who are eligible. 13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen at Screening 14. Used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) greater than the equivalent of 10 cigarettes per day during the one month prior to study start 15. Ppoor peripheral venous/arterial access 16. Donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 mo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of recalled items in the immediate and two delayed tests as well as correct answers in recognition part is measured using the verbal learning test (VLT) at 60 minutes (immediate recall), 110 minutes (delayed recall and recognition) and 1140 minutes (delayed recall and recognition 24 hours later). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Amplitude and latency of ERP’s are assessed during memorization phase of the VLT (ie, P300, N400, and P600) at 60 and 110 minutes 2. SMT outcome scores captured as the number of correctly localized items in the immediate and in the 2 delayed recalls and the recognition test at 75 (immediate recall), 20 (delayed recall) and 1450 minutes (delayed recall 24 hours later) 3. EEG measurements captured as the amplitude and latency of ERP’s (ie, P300, N400, and P600) during the SMT at 75 and 110 minutes. 4. Stroop task outcome scores captured as both the number of errors and reaction time and the amplitude and latency of ERP’s (ie, N200 and P300) at 85 and 1460 minutes (24 hours later) 5. EEG measurements captured as Mismatch Negativity (MMN) and P3a amplitude and latency during the Novelty oddball task at 125 minutes 6. EEG measurements captured as S2/S1 ratio and S1-S2 difference score of the P50 amplitude at sensory gating paradigm at 95 minutes 7. Cognitive improvement is measured by BL-VAS at baseline, 105, and 1435 minutes 8. Cmax and AUC of roflumilast and roflumilast N-oxide is measured by venipuncture at 70, 140, 1470 minutes (24 hours later). Blood samplesa re collected by certified study personnel by means of venipuncture. Blood samples are collected for measurement of roflumilast and roflumilast N-oxide concentrations at time points specified above. Plasma concentrations of roflumilast and roflumilast N-oxide were determined using a validated assay using high-performance liquid chromatography with tandem mass spectrometry. | — |
Countries
Netherlands
Contacts
Public ContactJos Prickaerts
Outcome results
None listed