Trial Outcomes & Findings for A Study to Assess the Effect of Repeat Doses of GSK962040 on the Pharmacokinetics of L-DOPA in Subjects With Parkinson's Disease Exhibiting Delayed Gastric Emptying (NCT NCT01602549)

Last Updated: 2017-02-06

Results Overview

Dose-normalized L-DOPA AUC(0-4) was derived from L-DOPA plasma concentration-time data. AUC is a measure of levodopa exposure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Baseline

Results posted on

2017-02-06

Participant Flow

The study consisted of a Screening/Baseline Period, a Treatment Period, and a 14-day post-treatment safety Follow-up Visit. Participants were randomized to receive GSK962040 50 milligrams or placebo in a 2:1 ratio; one participant was randomized to receive GSK962040 125 mg.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Overall Study STARTED	19	38
Overall Study COMPLETED	18	37
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

A Study to Assess the Effect of Repeat Doses of GSK962040 on the Pharmacokinetics of L-DOPA in Subjects With Parkinson's Disease Exhibiting Delayed Gastric Emptying

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.	Total n=57 Participants Total of all reporting groups
Age, Continuous	66.7 Years STANDARD_DEVIATION 8.04 • n=5 Participants	67.4 Years STANDARD_DEVIATION 7.97 • n=7 Participants	67.1 Years STANDARD_DEVIATION 7.93 • n=5 Participants
Gender Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Gender Male	8 Participants n=5 Participants	29 Participants n=7 Participants	37 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	19 Participants n=5 Participants	38 Participants n=7 Participants	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: Pharmacodynamic (PD)/Efficacy Population: participants receiving \>=1 dose placebo/GSK962040 50 mg. Only those participants available at the specified time point were analyzed.

Dose-normalized L-DOPA AUC(0-4) was derived from L-DOPA plasma concentration-time data. AUC is a measure of levodopa exposure.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=33 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Dose-normalized Levodopa (L-DOPA) Area Under the Plasma Concentration-time Curve From Zero to 4 Hours AUC(0-4) at Baseline	24.13 Nanograms*hour/milliliter/milligram Geometric Coefficient of Variation 37.5	24.81 Nanograms*hour/milliliter/milligram Geometric Coefficient of Variation 36.1	—

PRIMARY outcome

Timeframe: Day 1 and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Dose-normalized L-DOPA AUC(0-4) was derived from L-DOPA plasma concentration-time data. The adjusted means and ratios (GSK962040 50 mg: Placebo) were estimated using a mixed model fitting treatment, visit, treatment\*visit, Baseline L-dopa pharmacokinetic (PK) parameter, and Baseline gastric emptying half-time as fixed effects, and participant as a random effect. AUC is a measure of levodopa exposure

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Dose-normalized L-DOPA AUC(0-4) at Day 1 and Day 8 Day 1, n=17, 31	26.6 Nanograms*hour/milliliter/milligram Standard Error 0.058	25.7 Nanograms*hour/milliliter/milligram Standard Error 0.047	—
Dose-normalized L-DOPA AUC(0-4) at Day 1 and Day 8 Day 8, n=17, 32	27.1 Nanograms*hour/milliliter/milligram Standard Error 0.058	24.1 Nanograms*hour/milliliter/milligram Standard Error 0.047	—

PRIMARY outcome

Timeframe: Baseline

Population: PD/Efficacy Population. Only those participants available at the specified time point were analyzed.

Dose-normalized L-DOPA Cmax was derived from L-DOPA plasma concentration-time data.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=35 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Dose-normalized L-DOPA Maximum Observed Concentration (Cmax) at Baseline	12.77 Nanograms/milliliter/milligram Geometric Coefficient of Variation 28.0	12.89 Nanograms/milliliter/milligram Geometric Coefficient of Variation 42.6	—

PRIMARY outcome

Timeframe: Day 1 and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Dose-normalized L-DOPA Cmax was derived from L-DOPA plasma concentration-time data. The adjusted means and ratios were estimated using a mixed model fitting treatment, visit, treatment\*visit, Baseline L-dopa PK parameter, and Baseline gastric emptying half-time as fixed effects, and participant as a random effect.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Dose-normalized L-DOPA Cmax at Day 1 and Day 8 Day 1, n=18, 35	13.4 Nanograms/milliliter/milligram Standard Error 0.081	11.6 Nanograms/milliliter/milligram Standard Error 0.065	—
Dose-normalized L-DOPA Cmax at Day 1 and Day 8 Day 8, n=17, 35	11.6 Nanograms/milliliter/milligram Standard Error 0.083	11.8 Nanograms/milliliter/milligram Standard Error 0.065	—

PRIMARY outcome

Timeframe: Baseline, Day 1, and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

L-DOPA Tmax was derived from L-DOPA plasma concentration-time data.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
L-DOPA Time of Occurrence of Cmax (Tmax) at Baseline, Day 1,and Day 8 Baseline, n=17, 35	1.50 Hours Interval 0.3 to 3.6	2.00 Hours Interval 0.3 to 4.0	—
L-DOPA Time of Occurrence of Cmax (Tmax) at Baseline, Day 1,and Day 8 Day 1, n=18, 35	1.61 Hours Interval 0.5 to 3.4	1.50 Hours Interval 0.3 to 3.5	—
L-DOPA Time of Occurrence of Cmax (Tmax) at Baseline, Day 1,and Day 8 Day 8, n=17, 35	2.00 Hours Interval 0.5 to 3.5	1.55 Hours Interval 0.3 to 4.0	—

PRIMARY outcome

Timeframe: Baseline, Day 1, and Day 8

L-DOPA t1/2 was derived from L-DOPA plasma concentration-time data. This endpoint was not assessed because there were insufficient L-DOPA data/profiles to calculate this parameter.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Gastric half emptying time is the time taken for half the contents of the stomach to empty. Gastric emptying was measured using the 13C-oral breath test, which is a tracer method that utilizes 13C, a non-radioactive isotope. Basal breath samples were obtained after an overnight fast or otherwise after 4 hours of fasting following a light meal. On Day 1 and Day 8, participants were then dosed with GSK962040 and additional breath test samples were taken prior to administration of a 13C-labelled test meal. The test meal was consumed approximately 80 minutes later. After consumption of the test meal, breath samples were collected at pre-specified time points over an approximately 4 hour period following the test meal. For the duration of the breath test, no food or drink were allowed. The 13C breath content was determined by isotope ratio mass spectrometry. GE t1/2 was determined by using the cumulative percentage of the administered dose of 13C excreted in breath over 4 hours.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Gastric Half Emptying Time (GE t1/2) at Baseline (BL), Day 1, and Day 8 Baseline, n=19, 37	99.6 Minutes Standard Deviation 21.26	96.9 Minutes Standard Deviation 21.67	—
Gastric Half Emptying Time (GE t1/2) at Baseline (BL), Day 1, and Day 8 Day 1, n=19, 37	97.5 Minutes Standard Deviation 15.81	91.9 Minutes Standard Deviation 21.47	—
Gastric Half Emptying Time (GE t1/2) at Baseline (BL), Day 1, and Day 8 Day 8, n=17, 36	98.7 Minutes Standard Deviation 25.03	90.6 Minutes Standard Deviation 26.75	—

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8 at pre-levodopa dose

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

The MDS-UPDRS is used to assess the status of Parkinson's Disease. It has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living), Part III (motor examination), and Part IV (motor complications). Each part is made up of several questions, with each question given a score ranging from 0 (normal) to 4 (severe). Part I and Part II consist of 13 items each, and have a score ranging between 0 (normal) and 52 (severe). Part III consists of 33 items, and has a score ranging between 0 (normal) and 132 (severe). Part IV consists of 6 items, and has a score ranging between 0 (normal) and 24 (severe). The total score is the summed score of all four parts and ranges between 0 (normal) and 260 (severe). A higher score indicates more severe symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part I: Baseline, n=19, 37	9.1 Scores on a scale Standard Deviation 4.56	10.1 Scores on a scale Standard Deviation 6.17	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part I: Day 1, n=19, 37	10.1 Scores on a scale Standard Deviation 4.98	8.6 Scores on a scale Standard Deviation 5.12	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part I: Day 8, n=18, 36	10.0 Scores on a scale Standard Deviation 5.25	7.1 Scores on a scale Standard Deviation 4.67	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part II: Baseline, n=19, 37	14.9 Scores on a scale Standard Deviation 7.09	12.5 Scores on a scale Standard Deviation 6.33	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part II: Day 1, n=19, 37	16.1 Scores on a scale Standard Deviation 9.09	11.5 Scores on a scale Standard Deviation 6.54	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part II: Day 8, n=18, 36	15.3 Scores on a scale Standard Deviation 9.29	10.3 Scores on a scale Standard Deviation 6.37	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part III: Baseline, n=19, 37	42.2 Scores on a scale Standard Deviation 14.63	38.0 Scores on a scale Standard Deviation 18.95	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part III: Day 1, n=19, 37	40.4 Scores on a scale Standard Deviation 17.56	34.9 Scores on a scale Standard Deviation 17.97	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part III: Day 8, n=18, 36	44.2 Scores on a scale Standard Deviation 19.25	34.0 Scores on a scale Standard Deviation 17.46	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part IV: Baseline, n=19, 37	5.5 Scores on a scale Standard Deviation 2.70	5.3 Scores on a scale Standard Deviation 3.63	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part IV: Day 1, n=19, 37	5.9 Scores on a scale Standard Deviation 3.07	5.2 Scores on a scale Standard Deviation 3.61	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Part IV: Day 8, n=18, 36	5.7 Scores on a scale Standard Deviation 3.79	4.5 Scores on a scale Standard Deviation 3.41	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Total: Baseline, n=19, 37	71.7 Scores on a scale Standard Deviation 23.53	65.8 Scores on a scale Standard Deviation 27.02	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Total: Day 1, n=19, 37	72.5 Scores on a scale Standard Deviation 29.01	60.2 Scores on a scale Standard Deviation 25.90	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) Total: Day 8, n=18, 36	75.2 Scores on a scale Standard Deviation 34.27	55.9 Scores on a scale Standard Deviation 25.34	—

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8 at pre-dose and 120, 180, and 240 minutes (min) post-dose (PD); Follow-up visit (up to Day 25)

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Baseline, pre-dose, n=19, 37	42.2 Scores on a scale Standard Deviation 14.63	38.0 Scores on a scale Standard Deviation 18.95	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Baseline, 120 minutes post-dose, n=19, 37	33.1 Scores on a scale Standard Deviation 16.61	27.7 Scores on a scale Standard Deviation 16.04	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Baseline, 180 minutes post-dose, n=19, 36	30.3 Scores on a scale Standard Deviation 14.55	27.5 Scores on a scale Standard Deviation 14.21	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Baseline, 240 minutes post-dose, n=19, 37	31.6 Scores on a scale Standard Deviation 16.27	29.2 Scores on a scale Standard Deviation 16.62	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 1, pre-dose, n=19, 37	40.4 Scores on a scale Standard Deviation 17.56	34.9 Scores on a scale Standard Deviation 17.97	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 1,120 minutes post-dose, n=19, 37	32.3 Scores on a scale Standard Deviation 15.01	26.2 Scores on a scale Standard Deviation 16.25	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 1, 180 minutes post-dose, n=19, 37	31.0 Scores on a scale Standard Deviation 17.10	25.5 Scores on a scale Standard Deviation 18.04	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 1, 240 minutes post-dose, n=19, 37	32.7 Scores on a scale Standard Deviation 20.50	27.2 Scores on a scale Standard Deviation 17.68	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 8, pre-dose n=18, 36	44.2 Scores on a scale Standard Deviation 19.25	34.0 Scores on a scale Standard Deviation 17.46	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 8, 120 minutes post-dose, n=18, 36	32.3 Scores on a scale Standard Deviation 14.90	24.2 Scores on a scale Standard Deviation 14.24	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 8, 180 minutes post-dose, n=18, 36	33.3 Scores on a scale Standard Deviation 16.17	25.1 Scores on a scale Standard Deviation 14.27	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Day 8, 240 minutes post-dose, n=18, 36	37.1 Scores on a scale Standard Deviation 20.19	25.4 Scores on a scale Standard Deviation 15.27	—
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose) Follow-up, n=19, 37	30.3 Scores on a scale Standard Deviation 13.45	24.9 Scores on a scale Standard Deviation 11.79	—

SECONDARY outcome

Timeframe: Baseline, Days 1-8, Week 1 of Follow-up (Days 6 and 7 of Follow-up; up to Day 16), and Week 2 of Follow-up (Days 13 and 14 of Follow-up; up to Day 23)

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Participants were provided with the "ON/OFF" diary to capture details of the amount of awake time spent on/off of PD symptoms, and were asked to complete the diary daily. Participants checked the box most appropriate for their dominant motor state in the preceding 30-minute period. The catergories included: "ON" (including "ON without dyskinesia" and "ON with non-troublesome dyskinesia"), "ON" with troublesome dyskinesia (TD), and "OFF." For Baseline, data were collected for 2 days prior to Day 1, and the mean value of the 2 days was used.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 1 of FU: "ON," n=18, 36	11.00 hours Standard Deviation 3.309	12.13 hours Standard Deviation 3.134	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 1 of FU: "ON" without dyskinesia, n=18, 36	10.17 hours Standard Deviation 4.232	10.63 hours Standard Deviation 3.948	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Baseline: "ON," n=18, 37	11.21 hours Standard Deviation 3.602	11.31 hours Standard Deviation 3.021	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Baseline: "ON" without dyskinesia, n=18, 37	10.11 hours Standard Deviation 4.069	9.65 hours Standard Deviation 3.787	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Baseline: "ON" with non-TD, n=18, 37	1.10 hours Standard Deviation 1.787	1.66 hours Standard Deviation 2.956	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Baseline: "ON" with TD, n=18, 37	0.54 hours Standard Deviation 1.240	0.40 hours Standard Deviation 1.292	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Baseline: "OFF," n=18, 37	4.92 hours Standard Deviation 3.417	4.23 hours Standard Deviation 2.484	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Treatment period: "ON," n=18, 36	10.61 hours Standard Deviation 3.927	12.44 hours Standard Deviation 3.375	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Treatment period: "ON" without dyskinesia, n=18,36	9.82 hours Standard Deviation 4.042	10.47 hours Standard Deviation 4.479	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Treatment period: "ON" with non-TD, n=18, 36	0.79 hours Standard Deviation 1.875	1.98 hours Standard Deviation 2.987	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Treatment period: "ON" with TD, n=18, 36	0.47 hours Standard Deviation 1.548	0.59 hours Standard Deviation 1.985	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Treatment period: "OFF," n=18, 36	5.57 hours Standard Deviation 4.364	2.94 hours Standard Deviation 2.954	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 1 of FU: "ON" with non-TD, n=18, 36	0.83 hours Standard Deviation 1.933	1.50 hours Standard Deviation 2.369	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 1 of FU: "ON" with TD, n=18, 36	0.71 hours Standard Deviation 2.083	0.52 hours Standard Deviation 1.986	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 1 of FU: "OFF," n=18, 36	4.83 hours Standard Deviation 3.700	3.31 hours Standard Deviation 2.642	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 2 of FU: "ON," n=16, 32	11.34 hours Standard Deviation 3.580	11.69 hours Standard Deviation 3.562	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 2 of FU: "ON" without dyskinesia, n=16, 32	11.13 hours Standard Deviation 4.138	9.98 hours Standard Deviation 4.872	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 2 of FU: "ON" with non-TD, n=16, 32	0.22 hours Standard Deviation 0.875	1.70 hours Standard Deviation 2.838	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 2 of FU: "ON" with TD, n=16, 32	0.38 hours Standard Deviation 1.500	0.80 hours Standard Deviation 2.362	—
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up Week 2 of FU: "OFF," n=16, 32	4.47 hours Standard Deviation 3.601	3.36 hours Standard Deviation 2.857	—

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8 at pre-dose and 0, 30, 60, 90, 120, 180, and 240 minutes post-dose; Follow-up visit (up to Day 25)

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Participants were asked to alternatively tap two keys 30 centimeters apart in 1 minute in two trials with the most affected hand or the dominant hand in symmetric disease. The finger tapping was scored manually by the study staff. The finger-tapping assessment was repeated at eight separate time points (pre-dose, 0 min, 30 min, 60 min, 90 min, 120 min, 180 min, and 240 min post-dose) at each visit (Baseline, Day 1, and Day 8). At each time point, the mean of the two assessments was calculated.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and Days 1, 2, 3, 4, 5, 6, 7, 8, and 9

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

Various formulations of L-DOPA were utilized by participants for the treatment of Parkinson's Disease. The total daily L-DOPA equivalent dose was calculated as the sum of all L-DOPA equivalent doses for each L-DOPA-containing drug taken on the same day.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 9, n=0, 5	0.0 Milligrams Standard Deviation 0.0	235.0 Milligrams Standard Deviation 121.96	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Baseline, n=19, 37	113.2 Milligrams Standard Deviation 41.14	164.5 Milligrams Standard Deviation 119.66	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 1, n=19, 37	353.9 Milligrams Standard Deviation 174.85	368.6 Milligrams Standard Deviation 216.54	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 2, n=19, 36	465.8 Milligrams Standard Deviation 229.61	514.5 Milligrams Standard Deviation 300.44	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 3, n=19, 36	481.6 Milligrams Standard Deviation 243.79	516.9 Milligrams Standard Deviation 299.98	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 4, n=19, 36	481.6 Milligrams Standard Deviation 241.50	518.3 Milligrams Standard Deviation 313.07	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 5, n=19, 36	484.2 Milligrams Standard Deviation 243.13	503.0 Milligrams Standard Deviation 293.48	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 6, n=17, 36	516.2 Milligrams Standard Deviation 249.21	511.3 Milligrams Standard Deviation 307.31	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 7, n=17, 35	486.8 Milligrams Standard Deviation 247.51	499.6 Milligrams Standard Deviation 310.57	—
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 Day 8, n=17, 34	191.2 Milligrams Standard Deviation 175.43	281.3 Milligrams Standard Deviation 234.00	—

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8

Population: All Subjects Population (ASP): all participants who received \>=1 dose of study medication. Participants with available data (n=X, X in category titles) were analyzed.

Blood pressure measurements were taken at pre-dose and at 0 min (completion of meal) on Day 1 and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 SBP, Day 1: 0 min, n=19, 37, 38	-4.0 Millimeters of mercury Standard Deviation 12.05	-2.5 Millimeters of mercury Standard Deviation 18.66	-2.1 Millimeters of mercury Standard Deviation 18.58
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 SBP, Day 8: pre-dose, n=18, 36, 37	-2.8 Millimeters of mercury Standard Deviation 13.24	-3.9 Millimeters of mercury Standard Deviation 13.19	-3.7 Millimeters of mercury Standard Deviation 13.06
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 SBP, Day 8: 0 min, n=18, 36, 37	-3.4 Millimeters of mercury Standard Deviation 11.55	-1.0 Millimeters of mercury Standard Deviation 15.04	-1.1 Millimeters of mercury Standard Deviation 14.84
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 DBP, Day 1: 0 min, n=19, 37, 38	-5.4 Millimeters of mercury Standard Deviation 7.67	-0.9 Millimeters of mercury Standard Deviation 7.51	-0.7 Millimeters of mercury Standard Deviation 7.55
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 DBP, Day 8: pre-dose, n=18, 36, 37	-4.2 Millimeters of mercury Standard Deviation 6.88	-0.9 Millimeters of mercury Standard Deviation 8.54	-0.8 Millimeters of mercury Standard Deviation 8.48
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 DBP, Day 8: 0 min, n=18, 36, 37	-3.7 Millimeters of mercury Standard Deviation 5.81	0.9 Millimeters of mercury Standard Deviation 8.32	0.9 Millimeters of mercury Standard Deviation 8.21

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

Heart rate measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Heart Rate at Day 1 and Day 8 Day 8: pre-dose, n=18, 36, 37	-2.9 Beats per minute Standard Deviation 7.67	0.6 Beats per minute Standard Deviation 6.12	0.0 Beats per minute Standard Deviation 6.84
Change From Baseline in Heart Rate at Day 1 and Day 8 Day 1: 0 min, n=19, 37, 38	-2.2 Beats per minute Standard Deviation 7.30	0.8 Beats per minute Standard Deviation 9.19	0.5 Beats per minute Standard Deviation 9.26
Change From Baseline in Heart Rate at Day 1 and Day 8 Day 8: 0 min, n=18, 36, 37	-2.5 Beats per minute Standard Deviation 7.64	-0.5 Beats per minute Standard Deviation 6.80	-0.5 Beats per minute Standard Deviation 6.71

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 8. The Baseline value was the Day 1 pre-dose value. ECG findings were categorized as normal, abnormal - not clinically significant, and abnormal - clinically significant (CS), based on interpretation by the site.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 8: pre-dose, Normal, n=18, 36, 37	14 Participants	18 Participants	19 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 1: pre-dose, Normal, n=19, 37, 38	14 Participants	17 Participants	18 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 1: pre-dose, Abnormal - Not CS, n=19, 37, 38	5 Participants	19 Participants	19 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 1: pre-dose, Abnormal - CS, n=19, 37, 38	0 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 1: 0 min, Normal, n=19, 37, 38	12 Participants	16 Participants	16 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 1: 0 min, Abnormal - Not CS, n=19, 37, 38	7 Participants	20 Participants	21 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 1: 0 min, Abnormal - CS, n=19, 37, 38	0 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 8: pre-dose, Abnormal - Not CS, n=18, 36, 37	4 Participants	17 Participants	17 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 8: pre-dose, Abnormal - CS, n=18, 36, 37	0 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 8: 0 min, Normal, n=18, 36, 37	12 Participants	19 Participants	20 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 8: 0 min, Abnormal - Not CS, n=18, 36, 37	6 Participants	16 Participants	16 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 Day 8: 0 min, Abnormal - CS, n=18, 36, 37	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

ALB and TP measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Albumin (ALB) and Total Protein (TP) at Day 4 and Day 8 ALB, Day 4, n=18, 34, 35	0.06 Grams per liter Standard Deviation 2.313	-0.38 Grams per liter Standard Deviation 2.155	-0.37 Grams per liter Standard Deviation 2.124
Change From Baseline in Albumin (ALB) and Total Protein (TP) at Day 4 and Day 8 ALB, Day 8, n=18, 34, 35	0.11 Grams per liter Standard Deviation 2.220	-0.33 Grams per liter Standard Deviation 2.084	-0.29 Grams per liter Standard Deviation 2.065
Change From Baseline in Albumin (ALB) and Total Protein (TP) at Day 4 and Day 8 TP, Day 4, n=18, 30, 31	-0.3 Grams per liter Standard Deviation 3.28	-0.9 Grams per liter Standard Deviation 3.93	-1.0 Grams per liter Standard Deviation 3.97
Change From Baseline in Albumin (ALB) and Total Protein (TP) at Day 4 and Day 8 TP, Day 8, n=15, 31, 32	-0.0 Grams per liter Standard Deviation 3.24	-0.3 Grams per liter Standard Deviation 3.72	-0.3 Grams per liter Standard Deviation 3.66

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

ALP, ALT, AST, and GGT measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 ALP, Day 4, n=19, 33, 34	-0.8 International units per liter Standard Deviation 5.26	2.4 International units per liter Standard Deviation 14.14	2.2 International units per liter Standard Deviation 13.98
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 ALP, Day 8, n=18, 34, 35	-0.1 International units per liter Standard Deviation 7.66	1.4 International units per liter Standard Deviation 13.35	1.2 International units per liter Standard Deviation 13.21
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 ALT, Day 4, n=19, 33, 34	-6.4 International units per liter Standard Deviation 10.45	-5.9 International units per liter Standard Deviation 9.77	-7.1 International units per liter Standard Deviation 11.72
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 ALT, Day 8, n=18, 34, 35	-1.6 International units per liter Standard Deviation 6.88	-0.4 International units per liter Standard Deviation 5.46	-0.6 International units per liter Standard Deviation 5.57
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 AST, Day 4, n=19, 32, 33	0.2 International units per liter Standard Deviation 3.16	-1.2 International units per liter Standard Deviation 2.89	-1.3 International units per liter Standard Deviation 2.96
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 AST, Day 8, n=16, 31, 32	0.6 International units per liter Standard Deviation 4.55	1.0 International units per liter Standard Deviation 3.65	0.9 International units per liter Standard Deviation 3.63
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 GGT, Day 4, n=19, 33, 34	-0.8 International units per liter Standard Deviation 3.20	-0.8 International units per liter Standard Deviation 3.06	-0.9 International units per liter Standard Deviation 3.04
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8 GGT, Day 4, n=18, 33, 34	-0.1 International units per liter Standard Deviation 5.22	-1.0 International units per liter Standard Deviation 5.02	-1.0 International units per liter Standard Deviation 4.95

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

Calcium, chloride, CO2/BC, glucose, potassium, sodium, urea/BUN, and UA measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

Basophils, eosinophils, lymphocytes, monocytes, total ANC, and PC measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Basophils, Day 4, n=19, 34, 35	-0.003 Giga (10^9) cells per liter Standard Deviation 0.0200	-0.006 Giga (10^9) cells per liter Standard Deviation 0.0247	-0.006 Giga (10^9) cells per liter Standard Deviation 0.0244
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Basophils, Day 8, n=17, 35, 36	-0.006 Giga (10^9) cells per liter Standard Deviation 0.0153	-0.001 Giga (10^9) cells per liter Standard Deviation 0.0195	-0.001 Giga (10^9) cells per liter Standard Deviation 0.0192
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Eosinophils, Day 4, n=19, 34, 35	0.003 Giga (10^9) cells per liter Standard Deviation 0.1219	-0.031 Giga (10^9) cells per liter Standard Deviation 0.0584	-0.034 Giga (10^9) cells per liter Standard Deviation 0.0599
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Eosinophils, Day 8, n=17, 35, 36	-0.016 Giga (10^9) cells per liter Standard Deviation 0.0519	-0.001 Giga (10^9) cells per liter Standard Deviation 0.0466	0.000 Giga (10^9) cells per liter Standard Deviation 0.0467
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Lymphocytes, Day 4, n=19, 34, 35	0.093 Giga (10^9) cells per liter Standard Deviation 0.4326	0.044 Giga (10^9) cells per liter Standard Deviation 0.3592	0.033 Giga (10^9) cells per liter Standard Deviation 0.3592
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Lymphocytes, Day 8, n=17, 35, 36	-0.049 Giga (10^9) cells per liter Standard Deviation 0.3258	0.076 Giga (10^9) cells per liter Standard Deviation 0.5874	0.073 Giga (10^9) cells per liter Standard Deviation 0.5793
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Monocytes, Day 4, n=19, 34, 35	0.006 Giga (10^9) cells per liter Standard Deviation 0.1313	0.002 Giga (10^9) cells per liter Standard Deviation 0.0923	0.004 Giga (10^9) cells per liter Standard Deviation 0.0913
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Monocytes, Day 8, n=17, 35, 36	-0.004 Giga (10^9) cells per liter Standard Deviation 0.0860	-0.013 Giga (10^9) cells per liter Standard Deviation 0.0928	-0.013 Giga (10^9) cells per liter Standard Deviation 0.0916
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Total ANC , Day 4, n=19, 34, 35	0.021 Giga (10^9) cells per liter Standard Deviation 0.8866	0.392 Giga (10^9) cells per liter Standard Deviation 0.9480	0.406 Giga (10^9) cells per liter Standard Deviation 0.9377
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 Total ANC , Day 8, n=17, 35, 36	0.007 Giga (10^9) cells per liter Standard Deviation 0.8586	-0.114 Giga (10^9) cells per liter Standard Deviation 0.8500	-0.122 Giga (10^9) cells per liter Standard Deviation 0.8392
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 PC, Day 4, n=19, 34, 35	4.5 Giga (10^9) cells per liter Standard Deviation 18.45	3.6 Giga (10^9) cells per liter Standard Deviation 18.76	3.3 Giga (10^9) cells per liter Standard Deviation 18.53
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 PC, Day 8, n=17, 35, 36	1.8 Giga (10^9) cells per liter Standard Deviation 24.42	1.4 Giga (10^9) cells per liter Standard Deviation 22.97	0.7 Giga (10^9) cells per liter Standard Deviation 22.97

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

Hemoglobin and MCHC measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Day 4 and Day 8 Hemoglobin, Day 4, n=19, 34, 35	-2.3 Grams per liter Standard Deviation 6.53	-2.0 Grams per liter Standard Deviation 6.35	-2.3 Grams per liter Standard Deviation 6.44
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Day 4 and Day 8 Hemoglobin, Day 8, n=17, 35, 36	-2.4 Grams per liter Standard Deviation 4.27	-2.3 Grams per liter Standard Deviation 4.71	-2.2 Grams per liter Standard Deviation 4.64
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Day 4 and Day 8 MCHC, Day 4, n=13, 24, 24	-0.0 Grams per liter Standard Deviation 8.85	0.6 Grams per liter Standard Deviation 8.83	0.6 Grams per liter Standard Deviation 8.83
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Day 4 and Day 8 MCHC, Day 8, n=12, 25, 25	0.4 Grams per liter Standard Deviation 8.30	-2.3 Grams per liter Standard Deviation 8.47	-2.3 Grams per liter Standard Deviation 8.47

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

Hematocrit measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Hematocrit at Day 4 and Day 8 Day 4, n=19, 34, 35	-0.0059 proportion of 1 Standard Deviation 0.02331	-0.0059 proportion of 1 Standard Deviation 0.02029	-0.0067 proportion of 1 Standard Deviation 0.02051
Change From Baseline in Hematocrit at Day 4 and Day 8 Day 8, n=17, 35, 36	-0.0044 proportion of 1 Standard Deviation 0.01383	-0.0037 proportion of 1 Standard Deviation 0.01702	-0.0039 proportion of 1 Standard Deviation 0.01682

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

MCH measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at Day 4 and Day 8 Day 4, n=19, 34, 35	-0.12 Picograms Standard Deviation 0.464	-0.06 Picograms Standard Deviation 0.744	0.07 Picograms Standard Deviation 0.737
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at Day 4 and Day 8 Day 8, n=17, 35, 36	0.03 Picograms Standard Deviation 0.718	-0.20 Picograms Standard Deviation 0.832	0.19 Picograms Standard Deviation 0.826

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

MCV measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Mean Corpuscle Volume (MCV) at Day 4 and Day 8 Day 4, n=19, 34, 35	-0.13 Femtoliters Standard Deviation 1.945	-0.14 Femtoliters Standard Deviation 1.339	-0.17 Femtoliters Standard Deviation 1.334
Change From Baseline in Mean Corpuscle Volume (MCV) at Day 4 and Day 8 Day 8, n=17, 35, 36	0.72 Femtoliters Standard Deviation 1.322	-0.05 Femtoliters Standard Deviation 1.401	-0.06 Femtoliters Standard Deviation 1.381

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

RBC and WBC measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Red Blood Cell Count (RBC) and White Blood Cell Count (WBC) at Day 4 and Day 8 RBC, Day 4, n=19, 34, 35	-0.055 Giga (10^9) cells per liter Standard Deviation 0.2345	0.068 Giga (10^9) cells per liter Standard Deviation 0.2138	-0.074 Giga (10^9) cells per liter Standard Deviation 0.2140
Change From Baseline in Red Blood Cell Count (RBC) and White Blood Cell Count (WBC) at Day 4 and Day 8 RBC, Day 8, n=17, 35, 36	-0.073 Giga (10^9) cells per liter Standard Deviation 0.1270	0.041 Giga (10^9) cells per liter Standard Deviation 0.1752	-0.043 Giga (10^9) cells per liter Standard Deviation 0.1730
Change From Baseline in Red Blood Cell Count (RBC) and White Blood Cell Count (WBC) at Day 4 and Day 8 WBC, Day 4, n=19, 34, 35	0.140 Giga (10^9) cells per liter Standard Deviation 0.9284	0.390 Giga (10^9) cells per liter Standard Deviation 1.0592	0.392 Giga (10^9) cells per liter Standard Deviation 1.0437
Change From Baseline in Red Blood Cell Count (RBC) and White Blood Cell Count (WBC) at Day 4 and Day 8 WBC, Day 8, n=17, 35, 36	-0.036 Giga (10^9) cells per liter Standard Deviation 0.8961	-0.154 Giga (10^9) cells per liter Standard Deviation 0.9006	-0.161 Giga (10^9) cells per liter Standard Deviation 0.8886

SECONDARY outcome

Timeframe: Baseline, Day 4, and Day 8

Population: ASP. Participants with available data (n=X, X in category titles) were analyzed.

RET measurements were taken at pre-dose on Day 1 (Baseline), Day 4, and Day 8. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Reticulocytes (RET) at Day 4 and Day 8 RET, Day 4, n=16, 28, 29	0.000 Tera (10^12) cells per liter Standard Deviation 0.0075	0.002 Tera (10^12) cells per liter Standard Deviation 0.0093	0.001 Tera (10^12) cells per liter Standard Deviation 0.0098
Change From Baseline in Reticulocytes (RET) at Day 4 and Day 8 RET, Day 8, n=13, 28, 29	0.004 Tera (10^12) cells per liter Standard Deviation 0.0080	0.001 Tera (10^12) cells per liter Standard Deviation 0.0093	0.001 Tera (10^12) cells per liter Standard Deviation 0.0095

SECONDARY outcome

Timeframe: From the start of study medication until Follow-up (up to Day 25)

Population: All Subjects Population

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect, is associated with liver injury and impaired liver function, or are serious events as per the medical or scientific judgment.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any AE	17 Participants	23 Participants	24 Participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any SAE	2 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

GSK AUC(0-5.5) and AUC(0-inf) were derived from GSK962040 plasma concentration-time data. Only participants who received GSK962040 50 mg were analyzed. AUC is a measure of levodopa exposure. Data for AUC(0-inf) was analyzed and was only available for Day 1 and not for Day 8.

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=36 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
GSK962040 Area Under the Plasma Concentration-time Curve From Zero to 5.5 Hours (AUC[0-5.5] and Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC[0-inf]) at Days 1 and 8 AUC(0-5.5): Day 1	—	1632.5 Nanograms.hour/milliliter Geometric Coefficient of Variation 38.1	—
GSK962040 Area Under the Plasma Concentration-time Curve From Zero to 5.5 Hours (AUC[0-5.5] and Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC[0-inf]) at Days 1 and 8 AUC(0-5.5): Day 8	—	3036.9 Nanograms.hour/milliliter Geometric Coefficient of Variation 45.8	—
GSK962040 Area Under the Plasma Concentration-time Curve From Zero to 5.5 Hours (AUC[0-5.5] and Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC[0-inf]) at Days 1 and 8 AUC(0-inf): Day 1	—	2972.8 Nanograms.hour/milliliter Geometric Coefficient of Variation 49.2	—

SECONDARY outcome

Timeframe: Day 1

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

GSK962040 %AUCex was derived from GSK962040 plasma concentration-time data. %AUCex is the percentage of the AUC(0-inf) extrapolated from the last PK sample drawn to infinity. This parameter is only reported in conjunction with single-dose AUC(0-inf). Only participants who received GSK962040 50 mg were analyzed. AUC is a measure of levodopa exposure.

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=36 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
GSK962040 Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) at Day 1	—	41.64 Percentage Geometric Coefficient of Variation 28.9	—

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

GSK962040 Cmax was derived from GSK962040 plasma concentration-time data. Only participants who received GSK962040 50 mg were analyzed.

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=36 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
GSK962040 Cmax at Day1 and Day 8 Day 1	—	501.0 Nanograms/milliliter Geometric Coefficient of Variation 45.4	—
GSK962040 Cmax at Day1 and Day 8 Day 8	—	788.3 Nanograms/milliliter Geometric Coefficient of Variation 46.0	—

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: PD/Efficacy Population. Participants with available data (n=X, X in category titles) were analyzed.

GSK962040 tmax was derived from GSK962040 plasma concentration-time data. Only participants who received GSK962040 50 mg were analyzed.

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=36 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
GSK962040 Tmax at Day1 and Day 8 Day 1	—	0.750 Hours Interval 0.25 to 3.5	—
GSK962040 Tmax at Day1 and Day 8 Day 8	—	1.000 Hours Interval 0.25 to 3.72	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

GSK962040 50 mg

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

GSK962040 125 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=19 participants at risk Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 participants at risk Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 125 mg n=1 participants at risk Participants received GSK962040 125 milligrams (mg) administered orally once daily for 7 to 9 days.
Vascular disorders Circulatory collapse	0.00% 0/19 • Post-randomization adverse events include those that occured on or after the randomization date.	2.7% 1/37 • Post-randomization adverse events include those that occured on or after the randomization date.	0.00% 0/1 • Post-randomization adverse events include those that occured on or after the randomization date.
Injury, poisoning and procedural complications Ankle fracture	5.3% 1/19 • Post-randomization adverse events include those that occured on or after the randomization date.	0.00% 0/37 • Post-randomization adverse events include those that occured on or after the randomization date.	0.00% 0/1 • Post-randomization adverse events include those that occured on or after the randomization date.
Nervous system disorders Parkinson's disease	5.3% 1/19 • Post-randomization adverse events include those that occured on or after the randomization date.	0.00% 0/37 • Post-randomization adverse events include those that occured on or after the randomization date.	0.00% 0/1 • Post-randomization adverse events include those that occured on or after the randomization date.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/19 • Post-randomization adverse events include those that occured on or after the randomization date.	2.7% 1/37 • Post-randomization adverse events include those that occured on or after the randomization date.	0.00% 0/1 • Post-randomization adverse events include those that occured on or after the randomization date.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: pre-dose, n=19, 37	92.4 Finger taps per minute Standard Deviation 47.53	77.8 Finger taps per minute Standard Deviation 38.00	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 0 min, n=19, 35	91.2 Finger taps per minute Standard Deviation 49.84	80.1 Finger taps per minute Standard Deviation 35.28	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 30 min, n=19, 34	89.3 Finger taps per minute Standard Deviation 42.91	85.2 Finger taps per minute Standard Deviation 41.45	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 60 min, n=19, 36	88.6 Finger taps per minute Standard Deviation 42.32	89.3 Finger taps per minute Standard Deviation 45.32	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 90 min, n=19, 36	91.2 Finger taps per minute Standard Deviation 44.14	90.8 Finger taps per minute Standard Deviation 45.18	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 120 min, n=19, 37	92.6 Finger taps per minute Standard Deviation 40.99	92.0 Finger taps per minute Standard Deviation 43.37	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 180 min, n=19, 37	94.1 Finger taps per minute Standard Deviation 47.19	92.8 Finger taps per minute Standard Deviation 44.86	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Baseline: 240 min, n=19, 37	95.2 Finger taps per minute Standard Deviation 44.60	93.2 Finger taps per minute Standard Deviation 46.17	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: pre-dose, n=19, 36	92.3 Finger taps per minute Standard Deviation 43.44	85.1 Finger taps per minute Standard Deviation 40.05	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 0 min, n=19, 364	90.7 Finger taps per minute Standard Deviation 40.78	86.8 Finger taps per minute Standard Deviation 44.65	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 30 min, n=18, 35	93.4 Finger taps per minute Standard Deviation 43.95	92.4 Finger taps per minute Standard Deviation 49.92	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 60 min, n=18, 35	93.8 Finger taps per minute Standard Deviation 44.80	94.6 Finger taps per minute Standard Deviation 44.06	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 90 min, n=19, 34	97.7 Finger taps per minute Standard Deviation 50.46	91.4 Finger taps per minute Standard Deviation 42.09	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 120 min, n=19, 35	99.9 Finger taps per minute Standard Deviation 50.51	96.4 Finger taps per minute Standard Deviation 42.06	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 180 min, n=18, 36	99.0 Finger taps per minute Standard Deviation 49.44	92.3 Finger taps per minute Standard Deviation 41.01	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 1: 240 min, n=18, 36	98.2 Finger taps per minute Standard Deviation 51.97	97.6 Finger taps per minute Standard Deviation 48.40	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: pre-dose, n=18, 35	95.7 Finger taps per minute Standard Deviation 40.90	92.8 Finger taps per minute Standard Deviation 43.92	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 0 min, n=18, 35	92.0 Finger taps per minute Standard Deviation 44.30	91.1 Finger taps per minute Standard Deviation 42.90	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 30 min, n=18, 34	95.8 Finger taps per minute Standard Deviation 45.07	92.2 Finger taps per minute Standard Deviation 41.14	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 60 min, n=18, 35	94.6 Finger taps per minute Standard Deviation 46.80	93.2 Finger taps per minute Standard Deviation 39.01	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 90 min, n=18, 34	95.0 Finger taps per minute Standard Deviation 48.82	95.5 Finger taps per minute Standard Deviation 42.60	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 120 min, n=18, 35	97.2 Finger taps per minute Standard Deviation 47.67	97.4 Finger taps per minute Standard Deviation 42.34	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 180 min, n=18, 34	96.8 Finger taps per minute Standard Deviation 52.50	101.2 Finger taps per minute Standard Deviation 49.86	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Day 8: 240 min, n=18, 35	98.3 Finger taps per minute Standard Deviation 53.30	102.8 Finger taps per minute Standard Deviation 51.84	—
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up Follow-up: n=18, 35	104.4 Finger taps per minute Standard Deviation 48.13	105.7 Finger taps per minute Standard Deviation 56.59	—

Measure	Placebo n=19 Participants Participants received placebo administered orally once daily for 7 to 9 days.	GSK962040 50 mg n=37 Participants Participants received GSK962040 50 milligrams (mg) administered orally once daily for 7 to 9 days.	GSK962040 Total n=38 Participants Participants received GSK962040 50 milligrams (mg) (except for one participant who received GSK962040 125 mg) administered orally once daily for 7 to 9 days.
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Calcium, Day 4, n=19, 34, 35	0.010 Millimoles per liter Standard Deviation 0.0746	-0.009 Millimoles per liter Standard Deviation 0.0659	-0.011 Millimoles per liter Standard Deviation 0.0667
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Calcium, Day 8, n=18, 35, 36	0.026 Millimoles per liter Standard Deviation 0.0756	-0.018 Millimoles per liter Standard Deviation 0.0662	-0.017 Millimoles per liter Standard Deviation 0.0652
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Chloride, Day 4, n=19, 33, 34	-1.37 Millimoles per liter Standard Deviation 1.832	-0.42 Millimoles per liter Standard Deviation 2.346	-0.41 Millimoles per liter Standard Deviation 2.311
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Chloride, Day 8, n=18, 33, 34	0.39 Millimoles per liter Standard Deviation 2.570	0.52 Millimoles per liter Standard Deviation 1.734	0.53 Millimoles per liter Standard Deviation 1.710
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 CO2/BC, Day 4, n=9, 21, 22	-0.06 Millimoles per liter Standard Deviation 2.833	0.16 Millimoles per liter Standard Deviation 2.602	0.20 Millimoles per liter Standard Deviation 2.546
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 CO2/BC, Day 8, n=8, 22, 23	0.51 Millimoles per liter Standard Deviation 2.053	0.23 Millimoles per liter Standard Deviation 2.139	0.13 Millimoles per liter Standard Deviation 2.141
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Glucose, Day 4, n=19, 35, 36	1.14 Millimoles per liter Standard Deviation 2.944	0.14 Millimoles per liter Standard Deviation 1.198	0.15 Millimoles per liter Standard Deviation 1.185
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Glucose, Day 8, n=18, 36, 36	-0.03 Millimoles per liter Standard Deviation 0.865	0.09 Millimoles per liter Standard Deviation 0.594	-0.09 Millimoles per liter Standard Deviation 0.594
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Potassium, Day 4, n=19, 32, 33	0.008 Millimoles per liter Standard Deviation 0.3393	0.168 Millimoles per liter Standard Deviation 0.3408	0.151 Millimoles per liter Standard Deviation 0.3497
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Potassium, Day 8, n=16, 31, 32	0.055 Millimoles per liter Standard Deviation 0.3405	0.048 Millimoles per liter Standard Deviation 0.2897	0.043 Millimoles per liter Standard Deviation 0.2862
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Sodium, Day 4, n=19, 34, 35	-0.89 Millimoles per liter Standard Deviation 2.787	-0.56 Millimoles per liter Standard Deviation 1.779	-0.51 Millimoles per liter Standard Deviation 1.772
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Sodium, Day 8, n=18, 34, 35	1.39 Millimoles per liter Standard Deviation 3.202	0.21 Millimoles per liter Standard Deviation 1.647	0.29 Millimoles per liter Standard Deviation 1.690
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Urea/BUN, Day 4, n=17, 32, 33	-0.27 Millimoles per liter Standard Deviation 1.757	0.00 Millimoles per liter Standard Deviation 1.496	-0.02 Millimoles per liter Standard Deviation 1.477
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 Urea/BUN, Day 8, n=17, 34, 35	-0.63 Millimoles per liter Standard Deviation 1.318	0.13 Millimoles per liter Standard Deviation 1.308	0.14 Millimoles per liter Standard Deviation 1.289
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 UA, Day 4, n=16, 30, 31	-14.22 Millimoles per liter Standard Deviation 23.416	0.53 Millimoles per liter Standard Deviation 29.735	-0.78 Millimoles per liter Standard Deviation 30.127
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8 UA, Day 8, n=14, 29, 30	-1.56 Millimoles per liter Standard Deviation 22.601	6.39 Millimoles per liter Standard Deviation 30.819	6.17 Millimoles per liter Standard Deviation 30.306