Phase I Study to Evaluate KP405 in Healthy and Parkinson's Disease Patients

Clinical safety data from adverse event (AE) reporting

Clinical safety data from 12-lead electrocardiogram (ECG) machine will automatically calculate:

RR interval PR interval QRS complex QT interval QTcF (QT interval corrected for heart rate using Fridericia's formula) Heart rate (beats per minute)

Clinical safety data from cardiac Holter monitoring

Clinical safety data from supine blood pressure (mmHg)

Clinical safety data from pulse rate (beats per minute)

Clinical safety data from oral temperature (degrees Celcius)

Blood chemistry clinical safety data from blood samples. The measurements are:

Amylase BUN Creatinine Glucose Sodium Potassium Phosphate Chloride Calcium AST ALT GGT Alkaline phosphatase Total bilirubin Uric acid Albumin Total protein Lactate dehydrogenase

Haematology clinical safety data from blood samples. The measurements are:

Haemoglobin Haematocrit RBC count RBC indices (MCV, MCH, MCHC) Platelet count White blood cell count with differential

Clinical safety data from urinalysis (dipstick*). The following will be measured:

Glucose Bilirubin Ketone Specific Gravity Blood pH Protein Urobilinogen Nitrite Leukocyte Esterase

*Microscopic analysis if dipstick is abnormal

Drugs of abuse:

Amphetamines Barbiturates Benzodiazepines Cocaine Cannabinoids Opiates

Coagulation clinical safety data from blood samples. The measurements are:

Prothrombin time International normalisation ratio Activated partial thromboplastin time

Serology clinical safety data from blood samples. The measurements are:

Anti-HIV I/II Anti-HCV HBsAg

Alcohol measurements will be done as a breath test

As part of a full physical examination the height of the subjects will be measured (in meters)

As part of a full physical examination body weight of the subjects will be measured (in kilograms)

As part of a full physical examination assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular system, abdomen (liver and spleen), lymph nodes and extremities will be conducted

Clinical safety data from injection site reactions

Plasma PK concentrations including but not limited to: maximum plasma concentration (Cmax) (ng/ml)

Plasma PK concentrations including but not limited to: time to reach Cmax (tmax) (minutes)

Plasma PK concentrations including but not limited to: area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration () (ng/ml x hours)

Plasma PK concentrations including but not limited to: AUC from zero to infinity (AUC0-∞)(ng/ml x hours)

Plasma PK concentrations including but not limited to: AUC from zero to 24 hours () (ng/ml x hours)

Plasma PK concentrations including but not limited to: AUC from zero to 48 hours (AUC0-48h) (ng/ml x hours)

Plasma PK concentrations including but not limited to: half life (t1/2) (hours)

The pupillometry measurements will be completed in a room where ambient noise and lighting will be controlled and uniform. After resting for 5 minutes, and before and after receiving the study drug, the pupillometry measurements (repeated once) will be taken from each eye using a pupilometer with an opaque rubber cup covering one eye. Each pupillometry session measuring both eyes will be approximately 1 minute.

Absolute and relative power spectral densities (PSDs) calculated for each 1 second epoch (1-59 Hz bins). Also grouped into the standard EEG bandwidths: delta, theta, alpha, beta and gamma. Additionally, the PSD variables will be averaged across brain regions of interest, including frontal, central, parietal, temporal and occipital

The following questions will be asked:

• How hungry do you feel (from 'not hungry at all' to 'very hungry')?
• How full do you feel (from 'not full at all' to 'very full')?
• How satisfied do you feel (from 'completely empty' to 'I cannot eat more')?
• How much do you think you can eat now (from 'nothing at all' to 'a lot')?

"You are required to keep an up-to-date food diary for the next few days, recording everything you consume (all nutrition that passes your lips)"

The test meal model is an accepted experimental method for assessing the effects of an intervention on food intake in a laboratory setting.

In its simplest form, it involves offering participants an excess amount of pre-weighed food (a pasta-based meal), instructing participants to eat the test meal until they feel comfortably full, and then weighing the amount of food remaining once the participant has finished eating.13 The weight of food consumed can then be determined (±0.1 g) and from the nutritional information on the food packaging, energy intake (kJ) can be calculated.

This questionnaire consists of thirteen VAS questions and one multiple choice question which in sum examine the palatability of the test meal, the participants' motivation to eat, the general wellbeing and physiological sensations of the participants, and the reason why they stopped eating. The VAS questions are self-rated by the participant by putting a perpendicular marking on each of the thirteen 100 mm lines