evenwichtsproblemen Balance disorders
Conditions
Interventions
- 1 mg lorazepam
- 2 mg haloperidol
- placebo
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male and/or female subjects of non-childbearing potential over the age of 70 years (inclusive; healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests).;2. Body Mass Index (BMI) of 17.5 to 35 kg/m2; and a total body weight =>50 kg.;3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.;4. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. ;5. Mini-Mental State Examination (MMSE) score > 26 points at screening.
Exclusion criteria
Exclusion criteria: 1. Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).;2. Subjects presenting with orthostatic hypotension, in which orthostatic hypotension is defined as a decrease of 20 mmHg for systolic blood pressure or 10 mmHg for diastolic blood pressure 2 minutes after standing from a supine position.;3. Any condition possibly affecting drug absorption (eg, gastrectomy).;4. A positive urine drug screen.;5. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of Screening.;6. Treatment with an investigational drug within 3 months prior to screening or having participated in more than 4 investigational drug studies within 1 year prior to screening.;7. Use of (non- )prescription medications that are believed to affect subject safety or the overall results of the study following judgment by the investigator.;8. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening;9. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.;10. Physically unable to perform BalRoom tests, e.g. walking and standing tests.;11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.;12. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects directly involved in the conduct of the study.;13. Clinical significant abnormalities on ECG and or QTcF > 500ms.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pharmacodynamics BalRoom assessment: • Sensory weights (weighting factors of proprioceptive, visual and vestibular system). • Active dynamics of ankle joint (time delay (s), active stiffness (Nm/rad) and active damping (Nm/rad/s)). • Active dynamics of hip joint (time delay (s), active stiffness (Nm/rad) and active damping (Nm/rad/s)). • Force feedback (time constant (s) and stiffness (Nm/rad )) • Passive dynamics of ankle joint (passive stiffness (Nm/rad) and passive damping (Nm/rad/s)). • Passive dynamics of hip joint (passive stiffness (Nm/rad) and passive damping (Nm/rad/s)). Neurocart assessment: • Saccadic Eye Movements (saccadic reaction time, saccadic peak velocity (deg/sec), and saccadic inaccuracy). • Body Sway (antero-posterior sway (mm/2min)). • Smooth Pursuit (percentage of time the eyes of the subjects are in smooth pursuit of the target (%)). • Bond and Lader VAS (alertness, calmness, mood subscales (mm)). • Bowdle VAS (internal & external perception, feeling high )(mm)) • Adaptive Tracking (%). • Pharmaco-EEG ((a, β, δ, γ and * *power) Short physical performance battery: • Ability to maintain standing balance (yes/no) • 4-meter walking speed (m/s) • Sit-to-stand transfer (s) Other: • Serum prolactin concentrations • Handgrip strength (kg) 2. Pharmacokinetics • Cmax, Tmax, AUClast, AUC24, AUCinf, CL/F, Vz/F, t1/2. 3. Tolerability / safety Adverse events, vital signs measurements, 12-lead ECGs, physical examination findings and clinical safety laboratory measurement. | — |
Countries
Netherlands
Outcome results
None listed