Trial Outcomes & Findings for Exploratory Study to Investigate Cognition Function and Mobility in Individuals With Pain (NCT NCT02974114)

NCT ID: NCT02974114

Last Updated: 2018-08-28

Results Overview

Error adjusted SRT was one of the main outcomes of the Axon Sports Priming Application. The Axon Sports Priming Application is a computerized test performed on a tablet device that measures cognitive performance, namely psychomotor speed. Axon sports test assessment included 1. Pain-state assessment performed at Visit 2 (Day 2 pre-treatment assessment and post-treatment assessment 1hour \[hr\] ± 15 minutes \[mins\] post-dosing) and 2. Pain-free assessment performed at Visit 3 (Day 3).

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 21 participants
• Primary outcome timeframe: At Day 2 (pre and post-treatment) and Day 3 of the study
• Results posted on: 2018-08-28

Participant Flow

All participants were recruited at a single center from the United Kingdom.

A Total of 54 participants were screened, out of which 21 participants were randomized to the study, 5 participants were screening failure, 1 participant withdrew consent and 27 participants were not randomized due to other reasons (not specified).

Participant milestones

Measure	Paracetamol and Caffeine All the participants in this arm received test product (containing 500 milligram \[mg\] of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 milliliters (mL) of water.	Paracetamol All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets orally once with 200 mL of water.	Placebo All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets orally once with 200 mL of water.
Overall Study STARTED	6	7	8
Overall Study COMPLETED	6	6	6
Overall Study NOT COMPLETED	0	1	2

Reasons for withdrawal

Measure	Paracetamol and Caffeine All the participants in this arm received test product (containing 500 milligram \[mg\] of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 milliliters (mL) of water.	Paracetamol All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets orally once with 200 mL of water.	Placebo All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets orally once with 200 mL of water.
Overall Study Other (Not specified)	0	1	2

Baseline Characteristics

Exploratory Study to Investigate Cognition Function and Mobility in Individuals With Pain

Baseline characteristics by cohort

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets orally once with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets orally once with 200 mL of water.	Placebo n=8 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets orally once with 200 mL of water.	Total n=21 Participants Total of all reporting groups
Age, Continuous	27.8 Years STANDARD_DEVIATION 4.83 • n=5 Participants	30.0 Years STANDARD_DEVIATION 9.45 • n=7 Participants	40.0 Years STANDARD_DEVIATION 15.87 • n=5 Participants	33.2 Years STANDARD_DEVIATION 12.31 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: At Day 2 (pre and post-treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

Error adjusted SRT was one of the main outcomes of the Axon Sports Priming Application. The Axon Sports Priming Application is a computerized test performed on a tablet device that measures cognitive performance, namely psychomotor speed. Axon sports test assessment included 1. Pain-state assessment performed at Visit 2 (Day 2 pre-treatment assessment and post-treatment assessment 1hour [hr] ± 15 minutes [mins] post-dosing) and 2. Pain-free assessment performed at Visit 3 (Day 3).

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain Free State (Day 3) in Error Adjusted Simple Reaction Time (SRT) in the Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	0.05 milliseconds (msec) Interval 0.0 to 0.2	0.07 milliseconds (msec) Interval 0.0 to 0.8	0.06 milliseconds (msec) Interval 0.0 to 0.2
Change From Pain Free State (Day 3) in Error Adjusted Simple Reaction Time (SRT) in the Pain State (Day 2) Change from pain-free state at Day2 post-treatment	0.04 milliseconds (msec) Interval 0.0 to 0.4	0.01 milliseconds (msec) Interval 0.0 to 0.3	0.00 milliseconds (msec) Interval -0.2 to 0.1

PRIMARY outcome

Timeframe: At Day 2 (pre and post-treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

The reaction time of five-choice reaction time task (provided by Cambridge Cognition) was measured. In five-choice reaction time task, all the participants hold down a button at the bottom of the screen till a yellow spot appears in one of the five circles at the top of the screen. Participants then released the button and touch inside of the circle where the yellow spot appeared as quickly as they can. The median duration, between the onset of the stimulus and the release of the button, was recorded as reaction time. Calculated for correct, assessed trials where the stimulus appeared in any one of five locations.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Reaction Time in the Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	2.00 msec Interval -17.5 to 36.0	-1.75 msec Interval -41.0 to 170.5	-1.00 msec Interval -6.5 to 18.5
Change From Pain-free State (Day 3) in Reaction Time in the Pain State (Day 2) Change from pain-free state at Day2 post-treatment	25.75 msec Interval -11.5 to 83.5	12.50 msec Interval -65.5 to 26.0	-8.00 msec Interval -28.0 to 24.5

PRIMARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

OTS was a measure of executive function and takes approximately 10 minutes to complete. The participant was shown two displays containing three coloured balls. The displays were presented in such a way that they can easily be perceived as stacks of coloured balls held in stockings or socks suspended from a beam. There was a row of numbered boxes along the bottom of the screen. The test administrator first demonstrated to the participant how to use the balls in the lower display to copy the pattern in the upper display, and completed one demonstration problem, where the solution requires one move. The participant then completed three further problems, one each of two moves, three moves, and four moves. Next, the participant was shown further problems, and participants worked out in their head how many moves the solutions to these problems required, and then touch the appropriate box at the bottom of the screen to indicate their response.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Number of One Touch Stockings (OTS) of Cambridge Assessment Problems (on Which the First Box Choice Made Was Correct) in the Pain State (Day 2) Change from pain-free state at Day2 post-treatment	-1.83 OTS of correct first box choice Standard Deviation 1.941	2.17 OTS of correct first box choice Standard Deviation 1.835	-1.40 OTS of correct first box choice Standard Deviation 2.702
Change From Pain-free State (Day 3) in Number of One Touch Stockings (OTS) of Cambridge Assessment Problems (on Which the First Box Choice Made Was Correct) in the Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-2.67 OTS of correct first box choice Standard Deviation 3.077	0.00 OTS of correct first box choice Standard Deviation 1.095	-0.20 OTS of correct first box choice Standard Deviation 1.789

PRIMARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

AST was a measure of executive attention. The test displayed an arrow which can appear on either side of the screen and can point in either direction. Each trial displayed a cue at the top of the screen that indicates whether to press the right or left button. Some trials displayed congruent stimuli (e.g. arrow on the right side of the screen pointing to the right) whereas other trials display incongruent stimuli which require a higher cognitive demand (e.g. arrow on the right side of the screen pointing to the left). The AST congruency cost was the difference between the median latencies of response (from stimulus appearance to button press) on the trials that were congruent versus the trials that were incongruent. It was calculated by subtracting the median of congruent from incongruent latency. A positive score indicated response was faster on congruent trials and a negative score indicated response was faster on incongruent trials.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Attention Switching Task (AST) Congruency Cost in the Pain State (Day 2) Change from pain-free state at Day2 post-treatment	-8.25 msec Interval -44.0 to 43.5	23.00 msec Interval -5.0 to 104.0	22.50 msec Interval -171.5 to 113.5
Change From Pain-free State (Day 3) in Attention Switching Task (AST) Congruency Cost in the Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-3.25 msec Interval -44.5 to 46.5	46.25 msec Interval -22.5 to 99.5	2.50 msec Interval -4.0 to 113.5

PRIMARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

SWM task was a measure of working memory. The task involved number of coloured squares (boxes) being shown on the screen. The aim of this test was to find one blue token in the boxes shown to the participants by process of elimination and used these to fill up an empty column on the right-hand side of the screen. The number of boxes gradually increased up to a maximum of eight boxes to search and the colour and position of the boxes changed from trial to trial. SWM between errors was defined as times the participant revisited a box in which a token has previously been found. This was calculated for trials of four, six and eight tokens.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Spatial Working Memory (SWM) Between Errors in the Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-9.33 SWM between errors Standard Deviation 18.747	25.17 SWM between errors Standard Deviation 29.075	13.80 SWM between errors Standard Deviation 23.994
Change From Pain-free State (Day 3) in Spatial Working Memory (SWM) Between Errors in the Pain State (Day 2) Change from pain-free state at Day2 post-treatment	4.83 SWM between errors Standard Deviation 22.248	13.50 SWM between errors Standard Deviation 23.193	-9.80 SWM between errors Standard Deviation 32.920

PRIMARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

RVP task was measures of attention. A white box appeared in the centre of the computer screen, inside which digits, from 2 to 9, appeared in a pseudo-random order, at the rate of 100 digits per minute. Participants were requested to detect target sequences of digits (for example, 2-4-6, 3-5-7, 4-6-8) and to register responses using the press pad. The RVPA (A prime) was the signal detection measure of sensitivity to the target, regardless of response tendency (the expected range will be 0.00 to 1.00; bad to good). RVP metric was a measure of how good the subject was at detecting target sequences.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Rapid Visual Information Processing A Prime (RVPA) in the Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-0.04 msec Interval -0.1 to 0.0	0.00 msec Interval 0.0 to 0.0	-0.03 msec Interval -0.1 to 0.0
Change From Pain-free State (Day 3) in Rapid Visual Information Processing A Prime (RVPA) in the Pain State (Day 2) Change from pain-free state at Day2 post-treatment	-0.02 msec Interval -0.1 to 0.0	-0.01 msec Interval -0.1 to 0.0	0.00 msec Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At Day 2 (pre and post-treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

This task was a measure of grip strength. The participant held the dynamometer in their dominant hand and the arm was swung from above the head to by the side of the body. If the dominant arm or hand was painful then the non-dominant hand was used. The participant was instructed to assert maximum effort during the squeezing motion and maintain it for about 4 seconds using a metronome. Participant conducted the movement 4-times (1 practice effort and 3 test efforts) and there was a 1-minute recovery period between each effort.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Grip Force in Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-1.98 Kilogram (Kg) Standard Deviation 5.505	-3.87 Kilogram (Kg) Standard Deviation 3.792	-1.70 Kilogram (Kg) Standard Deviation 3.533
Change From Pain-free State (Day 3) in Grip Force in Pain State (Day 2) Change from pain-free state at Day2 post-treatment	0.68 Kilogram (Kg) Standard Deviation 2.384	-2.80 Kilogram (Kg) Standard Deviation 3.059	-0.46 Kilogram (Kg) Standard Deviation 1.365

SECONDARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

Time to standing provides a simple assessment of physical mobility. From a seated position with arms crossed so that the right hand is placed on the left shoulder and the left hand on the right shoulder, participants stood to a fully erect stature in as short a time as possible. Time to standing recorded which was measured using a stopwatch. Participants conducted the same movement 3-times continuously as a practice effort and 5-times continuously as a test effort at each visit. There was a 1-minute rest between the practice and test effort.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Time to Standing in Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	0.10 Seconds Interval -0.4 to 0.2	0.13 Seconds Interval -0.2 to 0.3	0.09 Seconds Interval 0.0 to 0.3
Change From Pain-free State (Day 3) in Time to Standing in Pain State (Day 2) Change from pain-free state at Day2 post-treatment	-0.01 Seconds Interval -0.2 to 0.5	-0.08 Seconds Interval -0.3 to 0.4	0.04 Seconds Interval -0.2 to 0.6

SECONDARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

From a seated position with arms crossed so that the right hand is placed on the left shoulder and the left hand on the right shoulder, participants stood to a fully erect stature in as short a time as possible. Participants conducted the same movement 3-times continuously as a practice effort and 5-times continuously as a test effort at each visit. There was a 1-minute rest between the practice and test effort. GRF was measured during the movement analyzed using a force plate interfaced with a computer.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Ground Reaction Force (GRF) in Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	3.35 Newtons Standard Deviation 11.781	-19.80 Newtons Standard Deviation 43.788	3.75 Newtons Standard Deviation 11.214
Change From Pain-free State (Day 3) in Ground Reaction Force (GRF) in Pain State (Day 2) Change from pain-free state at Day2 post-treatment	4.21 Newtons Standard Deviation 8.295	-13.85 Newtons Standard Deviation 47.387	3.08 Newtons Standard Deviation 12.064

SECONDARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

Participants performed a walking assessment in comfortable walking shoes to measure gait parameter contact phase. An athletic movement analysis system (Optojump, Microgate) was utilized which set up over a 15 meters (m) length of track with only the 5-10m section measured and analysed. Participants were instructed to walk the 15m length a minimum of 6 times (3 practice and a minimum of 3 test walks) always entering the 15m length with the same foot first. The foot (left or right) entering the 5-10m section first was recorded by visual assessment of the Optojump operator for the test walks. Test walks were repeated until there were 3 walks in which the participants have entered the 5-10m section with the same foot first.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Contact Phase in Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	0.03 Seconds Interval 0.0 to 0.1	0.03 Seconds Interval 0.0 to 0.1	0.00 Seconds Interval 0.0 to 0.0
Change From Pain-free State (Day 3) in Contact Phase in Pain State (Day 2) Change from pain-free state at Day2 post-treatment	0.03 Seconds Interval 0.0 to 0.1	0.02 Seconds Interval 0.0 to 0.1	0.01 Seconds Interval -0.02 to 0.03

SECONDARY outcome

Timeframe: At Day 2 (pre and post treatment) and Day 3 of the study

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

Participants performed a walking assessment in comfortable walking shoes to measure gait parameter stride length. An athletic movement analysis system (Optojump, Microgate) was utilized which set up over a 15 meters (m) length of track with only the 5-10m section measured and analysed. Participants were instructed to walk the 15m length a minimum of 6 times (3 practice and a minimum of 3 test walks) always entering the 15m length with the same foot first. The foot (left or right) entering the 5-10m section first was recorded by visual assessment of the Optojump operator for the test walks. Test walks were repeated until there were 3 walks in which the participants have entered the 5-10m section with the same foot first.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Stride Length in Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-0.06 Centimeter Standard Deviation 0.098	-0.08 Centimeter Standard Deviation 0.123	-0.02 Centimeter Standard Deviation 0.038
Change From Pain-free State (Day 3) in Stride Length in Pain State (Day 2) Change from pain-free state at Day2 post-treatment	-0.04 Centimeter Standard Deviation 0.084	-0.06 Centimeter Standard Deviation 0.116	-0.04 Centimeter Standard Deviation 0.037

SECONDARY outcome

Timeframe: At Day 2 (pre and post-treatment) and Day 3

Population: Modified Intent-to-Treat (mITT, N=20) Population: All the participants who were randomized, received at least one dose of the study treatment and had at least one post-baseline assessment without any violation of study inclusion-exclusion criteria were included in the mITT population.

Participants performed a walking assessment in comfortable walking shoes to measure gait parameter walking speed over 5-10m for each foot. An athletic movement analysis system (Optojump, Microgate) was utilized which set up over a 15 meters (m) length of track with only the 5-10m section measured and analysed. Participants were instructed to walk the 15m length a minimum of 6 times (3 practice and a minimum of 3 test walks) always entering the 15m length with the same foot first. The foot (left or right) entering the 5-10m section first was recorded by visual assessment of the Optojump operator for the test walks. Test walks were repeated until there were 3 walks in which the participants have entered the 5-10m section with the same foot first.

Outcome measures

Measure	Paracetamol and Caffeine n=6 Participants All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 Participants All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=7 Participants All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Change From Pain-free State (Day 3) in Walking Speed in Pain State (Day 2) Change from pain-free state at Day 2 pre-treatment	-0.11 meters/second Standard Deviation 0.112	-0.10 meters/second Standard Deviation 0.180	-0.02 meters/second Standard Deviation 0.052
Change From Pain-free State (Day 3) in Walking Speed in Pain State (Day 2) Change from pain-free state at Day2 post-treatment	-0.10 meters/second Standard Deviation 0.105	-0.07 meters/second Standard Deviation 0.157	-0.03 meters/second Standard Deviation 0.043

Adverse Events

Paracetamol and Caffeine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Paracetamol

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Paracetamol and Caffeine n=6 participants at risk All the participants in this arm received test product (containing 500 mg of paracetamol and 65 mg of caffeine). All the participants took 2 tablets at once orally with 200 mL of water.	Paracetamol n=7 participants at risk All the participants in this arm received test product (containing 500 mg of paracetamol). All the participants took 2 tablets at once orally with 200 mL of water.	Placebo n=8 participants at risk All the participants in this arm received reference product (placebo to match Paracetamol 665mg sustained release tablets). All the participants took 2 tablets at once orally with 200 mL of water.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/6 • Up to 61 days	14.3% 1/7 • Up to 61 days	0.00% 0/8 • Up to 61 days
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/6 • Up to 61 days	0.00% 0/7 • Up to 61 days	12.5% 1/8 • Up to 61 days
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/6 • Up to 61 days	0.00% 0/7 • Up to 61 days	12.5% 1/8 • Up to 61 days

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: GSKClinicalSupportHD@gsk.com

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