Trial Outcomes & Findings for A Safety, Tolerability and Levodopa Pharmacokinetics Study of Repeated ND0612 in Parkinson's Disease Patients (NCT NCT01883505)

A Safety, Tolerability and Levodopa Pharmacokinetics Study of Repeated ND0612 in Parkinson's Disease Patients

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. Draize score is the sum of the erythema and eschar formation plus edema scores with 0 meaning no and 8 indicating the most severe erythema, eschar, and edema formation. The maximum dermal rating score was assessed in Period 1.

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. Erythema was evaluated via the Draize score on a scale of 0 to 4, with 0 meaning no erythema to a maximum score of 4 representing the most severe erythema (beet redness to eschar formation). The maximum dermal rating score was assessed in Period 1.

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. Edema was evaluated via the Draize score on a scale of 0 to 4, with 0 meaning no edema to a maximum score of 4 representing the most severe edema (raised more than 1 mm and extending beyond the area of exposure). The maximum dermal rating score was assessed in Period 1.

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. Evaluated via a scale of 0 to 3, with 0 meaning no nodule to a score of 3 representing severe (\> 1 cm). The maximum dermal rating score was assessed in Period 1.

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. Evaluated on a scale of 0 to 3, with 0 meaning no pruritus to a maximum score of 3 representing severe pruritus. The maximum dermal rating score was assessed in Period 1.

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. The presence of staining at the infusion site was evaluated via a scale of 0 to 3, with 0 meaning none to a score of 3 representing severe. The maximum dermal rating score was assessed in Period 1.

Local safety of the infusion sites was comprehensively assessed approximately one hour after removal of the SC pump. Pain score was evaluated with a visual analog scale (VAS). The VAS was a horizontal line, 100 mm in length, anchored by word descriptors at each end; "no pain" = 0 mm to "very severe pain" = 100 mm. The patient marked on the line the point that they felt represented their current state. The maximum dermal rating score was assessed in Period 1.

Total oral levodopa dose during PK sampling day

The lowest plasma concentration (Cmin) measured during a sampling period. Samples collected at 2 h and 1 h prior to the first morning oral LD dose, and every 30 min for 2 h then hourly until 10 h.

Maximum observed levodopa plasma concentration (Cmax). Samples collected at 2 h and 1 h prior to the first morning oral LD dose, and every 30 min for 2 h then hourly until 10 h.

Area under the concentration-time curve (AUC) until 10 h. Samples collected at 2 h and 1 h prior to the first morning oral LD dose, and every 30 min for 2 h then hourly until 10 h.

Time LD plasma concentrations were maintained above 1000 ng/mL. Samples collected at 2 h and 1 h prior to the first morning oral LD dose, and every 30 min for 2 h then hourly until 10 h.

LD plasma concentration Fluctuation index (FI) is a pharmacokinetic parameter defined as \[Cmax-Cmin\]/Caverage. Samples collected at 2 h and 1 h prior to the first morning oral LD dose, and every 30 min for 2 h then hourly until 10 h. Lower values are considered better to maintain the clinical response.

Daily OFF time change from Baseline based on ON-OFF home diaries. Daily OFF time at each time point (Baseline and Day 14) is calculated as a mean value of daily OFF time over 3 days preceding the respective time points. Hence, the outcome measure is the difference between those mean values.

The UPDRS consists of 4 parts: Part I (questions 1 to 4) is used to rate mentation, behavior, and mood collected as historical information without direct relevance to ON-OFF periods experienced by the patient; Part II (questions 5 to 17) is used to rate activities of daily living collected as historical information; Part III (questions 18 to 31) evaluates motor skills and ability at the time of the study visit when the scale is used; Part IV (questions 32 to 42) evaluates dyskinesias, clinical fluctuations, and other complications (anorexia, nausea, vomiting, sleep disturbances, orthostasis). UPDRS Total score ranges from 0 to 176 (higher scores are associated with more disability).

Parkinson's Disease Sleep Scale (PDSS) is a 15-item questionnaire that addresses overall quality of night sleep, sleep onset and maintenance insomnia, nocturnal restlessness, nocturnal psychosis, nocturia, nocturnal motor symptoms, sleep refreshment, and daytime dosing. Scores are obtained using a VAS. PDSS score ranges from 0 to 150 (lower scores indicate improvement).

The 39-item PD questionnaire (PDQ-39) was used to determine the patient's personal assessment of how often, due to their PD, they had experienced the problem defined by each item such as physical activity, emotional status, and mental status (never, occasionally, sometimes, often, always). PDQ-39 score ranges from 0 to 100 (lower scores indicate improvement).

Clinical Global Impression of Change (CGI-C) is a scale from 1 to 7 for a clinician to answer the question "Rate total improvement whether or not, in your judgment, it is due entirely to drug treatment?" where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.