Common Cold
Conditions
Keywords
alertness
Brief summary
This study will investigate any improvement in alertness and performance based on cognitive function and mood assessment in subjects suffering the common cold, when taking a novel paracetamol and caffeine combination verses paracetamol alone.
Interventions
DRUGparacetamol + caffeine
paracetamol with caffeine
DRUGparacetamol
paracetamol
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with symptoms of cold \< 96 hours, rating of at least '2' on malaise at least 4 other symptoms of cold. * No history of clinically significant perennial rhinitis, no recent antibiotic, antihistamine or cold treatment, no caffeine in the previous 12 hours, no psychoactive medication in the 14 days prior to screening, no pregnancy, breastfeeding or participation in this trial, or another trial in the 30 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Number of Accurate Responses to Rapid Visual Information Processing (RVIP) Cognitive Test | Baseline to 60 minutes post treatment administration | The RVIP assessed the performance of visual attention mechanisms in remaining vigilant to periodically occurring events. The number of accurate responses to RVIP task was determined from the cognitive function computerised output. Participants monitored a series of single numbers (0-9) appearing in the centre of the screen. During the RVIP task, participants responded to consecutive sequences of three odd or three even numbers by pressing the corresponding response button as quickly and accurately as possible. This was identified in the output file by a value of '1' in 'TARGET=1' column. Also, the response time (in seconds) was recorded in the 'RT' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'. The test lasted approximately 9 minutes and number of accurate responses to stimulus was calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | Baseline, 60 minutes and upto 120 minutes post treatment administration | The mean time of accurate responses was defined as the mean reaction time for the correct responses. For records with '1' in the 'CORRECT=1' column, the mean time of accurate response was calculated as the summation of the response time values divided by number of records with '1' in the 'CORRECT=1' column. The result was multiplied by 1000 to convert into milliseconds (msecs). |
| Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Baseline, 60 minutes and up to 120 minutes post treatment administration | The no. of inaccurate responses to RVIP was determined from cognitive function computerised output. Participants monitored a series of single numbers (0-9) appearing in the centre of screen. They responded to consecutive sequences of 3 odd or even numbers by pressing the corresponding response button. This was identified in the output file by a value of '1' in the 'TARGET=1' column. If a subject responded incorrectly to stimuli (pressed the response button at the wrong time), this was identified by a value of '-1' in the 'CORRECT=1' column. The no. of incorrect responses was calculated as the total no. of records where 'CORRECT=1' had a value of '-1'. If the subject missed a target (failed to press the response button within 600 msecs of being presented with a string of 3 consecutive even or odd numbers), this was considered a missed response and was calculated as the no. of records where there was a value of '1' in the 'TARGET=1' column and a value of '0' in the 'CORRECT=1' column. |
| Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Baseline, 60 minutes and up to 120 minutes post treatment administration | Auditory and visual attention of participants was evaluated using a validated Sustained Attention task. For the sustained auditory attention task, participants were required to respond whenever they heard the number '8' in a continuous stream of numbers presented through headphones. This was identified in the output file by a value of '8' in the 'NUMBER' column. For the sustained visual attention task, participants were required to respond to the letter 's' every time it appeared in a continuous stream of letters presented on a screen. This was identified in the output file by a value of 's' in the 'LETTER' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'. |
| Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | Baseline, 30 minutes and up to 60 minutes post treatment administration | The mean time of accurate responses was defined as the mean reaction time for the correct responses. For records with '1' in the 'CORRECT=1' column, the mean time of accurate response was calculated as the summation of the response time values divided by number of records with '1' in the 'CORRECT=1' column. The result was multiplied by 1000 to convert into milliseconds (msecs). |
| Change From Baseline in Number of Accurate Responses to RVIP Cognitive Test | Baseline to 120 minutes post treatment administration | The RVIP assessed the performance of visual attention mechanisms in remaining vigilant to periodically occurring events. The number of accurate responses to RVIP task was determined from the cognitive function computerised output. Participants monitored a series of single numbers (0-9) appearing in the centre of the screen. During the RVIP task, participants responded to consecutive sequences of three odd or three even numbers by pressing the corresponding response button as quickly and accurately as possible. This was identified in the output file by a value of '1' in 'TARGET=1' column. Also, the response time (in seconds) was recorded in the 'RT' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'. The test lasted approximately 9 minutes and number of accurate responses to stimulus was calculated. |
| Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | Baseline, 60 minutes and up to 120 minutes post treatment administration | Auditory and visual attention of participants was evaluated using a validated Divided Attention task. Participants were required to respond whenever they heard the number '8' in a continuous stream of numbers presented through headphones or saw a letter 's' on the screen . This was identified in the output file by a value of '8' in the 'NUMBER' column or by a value of 's' in the 'LETTER' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'. |
| Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | Baseline, 60 minutes and up to 120 minutes post treatment administration | The mean time of accurate responses was defined as the mean reaction time for the correct responses. For records with '1' in the 'CORRECT=1' column, the mean time of accurate response was calculated as the summation of the response time values divided by number of records with '1' in the 'CORRECT=1' column. The result was multiplied by 1000 to convert into milliseconds (msecs). |
| Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Baseline, 60 minutes and up to 120 minutes post treatment administration | For the Divided Attention task, participants were required to respond on hearing the no. '8' in a continuous stream of numbers through headphones or seeing a letter 's' on screen. This was identified in the output file by a value of '8' in 'NUMBER' column or 's' in 'LETTER' column. If a subject responded incorrectly (pressed the response button at the wrong time), this was identified by a value of '-1' in 'CORRECT=1' column. The number of incorrect responses was calculated as the total no. of records where 'CORRECT=1' had a value of '-1'. If the subject missed a target (failed to press the response button on hearing the no. '8' or seeing the letter 's'), this was considered a missed response. The number of missed responses was calculated as the no. of records where there was a value of '8' in 'NUMBER' column or 's' in 'LETTER' column and a value of '0' in the 'CORRECT=1' column. |
| Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Baseline, 60 minutes and up to 120 minutes post treatment administration | For sustained auditory attention task, participants were required to respond on hearing the no. '8' in a continuous stream of numbers through headphones. It was identified in output file by a value of '8' in 'NUMBER' column. For sustained visual attention task, participants responded to letter 's' every time it appeared in a continuous stream of letters presented on screen. This was identified in output file by a value of 's' in 'LETTER' column. If a subject responded incorrectly (pressed the response button at the wrong time), it was identified by a value of '-1' in 'CORRECT=1' column. The no. of incorrect responses was calculated as total no. of records where 'CORRECT=1' had a value of '-1'. The no. of missed responses (when subject failed to press the response button on hearing the number '8' or seeing the letter 's'), was calculated as the no. of records where there was a value of '8' in 'NUMBER' column or 's' in the 'LETTER' column and a value of '0' in the 'CORRECT=1' column. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Out of 244 participants screened, 4 did not meet the study criteria. Remaining 240 were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Paracetamol + Caffeine Combination (1000/130) Two paracetamol (500 mg) and caffeine (65 mg) tablets were dissolved in 200 mL of water and administered orally. | 46 |
| Paracetamol (1000) Two paracetamol tablets (500 mg each) were dissolved in 200 mL of water and administered orally. | 45 |
| Paracetamol + Caffeine Combination (500/65) One paracetamol (500 mg) and caffeine (65 mg) tablet was dissolved in 200 mL of water and administered orally. | 74 |
| Paracetamol (500) One paracetamol tablet (500 mg) was dissolved in 200 mL of water and administered orally. | 75 |
| Total | 240 |
Baseline characteristics
| Characteristic | Paracetamol + Caffeine Combination (1000/130) | Paracetamol (1000) | Paracetamol + Caffeine Combination (500/65) | Paracetamol (500) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 20.0 Years STANDARD_DEVIATION 1.56 | 20.0 Years STANDARD_DEVIATION 1.74 | 20.6 Years STANDARD_DEVIATION 4.19 | 20.2 Years STANDARD_DEVIATION 2.8 | 20.2 Years STANDARD_DEVIATION 2.98 |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 47 Participants | 48 Participants | 154 Participants |
| Sex: Female, Male Male | 15 Participants | 17 Participants | 27 Participants | 27 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 46 | 0 / 45 | 0 / 74 | 0 / 75 |
| serious Total, serious adverse events | 0 / 46 | 0 / 45 | 0 / 74 | 0 / 75 |
Outcome results
Primary
Change From Baseline in Number of Accurate Responses to Rapid Visual Information Processing (RVIP) Cognitive Test
The RVIP assessed the performance of visual attention mechanisms in remaining vigilant to periodically occurring events. The number of accurate responses to RVIP task was determined from the cognitive function computerised output. Participants monitored a series of single numbers (0-9) appearing in the centre of the screen. During the RVIP task, participants responded to consecutive sequences of three odd or three even numbers by pressing the corresponding response button as quickly and accurately as possible. This was identified in the output file by a value of '1' in 'TARGET=1' column. Also, the response time (in seconds) was recorded in the 'RT' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'. The test lasted approximately 9 minutes and number of accurate responses to stimulus was calculated.
Time frame: Baseline to 60 minutes post treatment administration
Population: Intent to Treat (ITT) population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Accurate Responses to Rapid Visual Information Processing (RVIP) Cognitive Test | 8.3 Correct responses | Standard Error 1.12 |
| Paracetamol (1000) | Change From Baseline in Number of Accurate Responses to Rapid Visual Information Processing (RVIP) Cognitive Test | 4.8 Correct responses | Standard Error 1.12 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Accurate Responses to Rapid Visual Information Processing (RVIP) Cognitive Test | 4.5 Correct responses | Standard Error 0.89 |
| Paracetamol (500) | Change From Baseline in Number of Accurate Responses to Rapid Visual Information Processing (RVIP) Cognitive Test | 2.7 Correct responses | Standard Error 0.88 |
Comparison: Null hypothesis was no difference in treatments in the change from baseline in the number of valid responses from the RVIP.p-value: 0.024895% CI: [0.4, 6.5]ANCOVA
Comparison: Null hypothesis was no difference in treatments in the change from baseline in the number of valid responses from the RVIP.p-value: 0.151395% CI: [-0.6, 4.1]ANCOVA
Comparison: Null hypothesis was no difference in treatments in change from baseline in number of valid responses from RVIP task.95% CI: [1.1, 6.6]ANCOVA
Secondary
Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test
The mean time of accurate responses was defined as the mean reaction time for the correct responses. For records with '1' in the 'CORRECT=1' column, the mean time of accurate response was calculated as the summation of the response time values divided by number of records with '1' in the 'CORRECT=1' column. The result was multiplied by 1000 to convert into milliseconds (msecs).
Time frame: Baseline, 60 minutes and up to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 60 minutes | -3.0 msec | Standard Error 2.94 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 120 minutes | -11.0 msec | Standard Error 3 |
| Paracetamol (1000) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 120 minutes | -5.3 msec | Standard Error 3 |
| Paracetamol (1000) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 60 minutes | 1.5 msec | Standard Error 2.94 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 60 minutes | -4.4 msec | Standard Error 2.33 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 120 minutes | -8.0 msec | Standard Error 2.37 |
| Paracetamol (500) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 60 minutes | -2.2 msec | Standard Error 2.28 |
| Paracetamol (500) | Change From Baseline in Mean Time of Accurate Responses to DAT Cognitive Test | 120 minutes | -4.6 msec | Standard Error 2.34 |
Secondary
Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task
The mean time of accurate responses was defined as the mean reaction time for the correct responses. For records with '1' in the 'CORRECT=1' column, the mean time of accurate response was calculated as the summation of the response time values divided by number of records with '1' in the 'CORRECT=1' column. The result was multiplied by 1000 to convert into milliseconds (msecs).
Time frame: Baseline, 60 minutes and upto 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 60 minutes | -1.4 milliseconds (msec) |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 120 minutes | -10.3 milliseconds (msec) |
| Paracetamol (1000) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 60 minutes | 2.4 milliseconds (msec) |
| Paracetamol (1000) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 120 minutes | -6.0 milliseconds (msec) |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 60 minutes | -0.9 milliseconds (msec) |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 120 minutes | -12.5 milliseconds (msec) |
| Paracetamol (500) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 120 minutes | -14.0 milliseconds (msec) |
| Paracetamol (500) | Change From Baseline in Mean Time of Accurate Responses to RVIP Cognitive Task | 60 minutes | -9.9 milliseconds (msec) |
Secondary
Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task
The mean time of accurate responses was defined as the mean reaction time for the correct responses. For records with '1' in the 'CORRECT=1' column, the mean time of accurate response was calculated as the summation of the response time values divided by number of records with '1' in the 'CORRECT=1' column. The result was multiplied by 1000 to convert into milliseconds (msecs).
Time frame: Baseline, 30 minutes and up to 60 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 60 minutes | -16.7 msec | Standard Error 3.17 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 120 minutes | -21.2 msec | Standard Error 3.48 |
| Paracetamol (1000) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 60 minutes | -9.8 msec | Standard Error 3.17 |
| Paracetamol (1000) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 120 minutes | -10.4 msec | Standard Error 3.48 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 60 minutes | -10.8 msec | Standard Error 2.51 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 120 minutes | -18.0 msec | Standard Error 2.74 |
| Paracetamol (500) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 120 minutes | -15.4 msec | Standard Error 2.72 |
| Paracetamol (500) | Change From Baseline in Mean Time of Accurate Responses to SAT Cognitive Task | 60 minutes | -12.0 msec | Standard Error 2.47 |
Secondary
Change From Baseline in Number of Accurate Responses to RVIP Cognitive Test
The RVIP assessed the performance of visual attention mechanisms in remaining vigilant to periodically occurring events. The number of accurate responses to RVIP task was determined from the cognitive function computerised output. Participants monitored a series of single numbers (0-9) appearing in the centre of the screen. During the RVIP task, participants responded to consecutive sequences of three odd or three even numbers by pressing the corresponding response button as quickly and accurately as possible. This was identified in the output file by a value of '1' in 'TARGET=1' column. Also, the response time (in seconds) was recorded in the 'RT' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'. The test lasted approximately 9 minutes and number of accurate responses to stimulus was calculated.
Time frame: Baseline to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Accurate Responses to RVIP Cognitive Test | 7.3 Correct responses | Standard Error 1.16 |
| Paracetamol (1000) | Change From Baseline in Number of Accurate Responses to RVIP Cognitive Test | 4.4 Correct responses | Standard Error 1.15 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Accurate Responses to RVIP Cognitive Test | 6.2 Correct responses | Standard Error 0.91 |
| Paracetamol (500) | Change From Baseline in Number of Accurate Responses to RVIP Cognitive Test | 3.5 Correct responses | Standard Error 0.92 |
Comparison: Null hypothesis was no difference in treatments in the change from baseline in the number of accurate responses from the RVIP.p-value: 0.069695% CI: [-0.2, 6.1]ANCOVA
Comparison: Null hypothesis was no difference in treatments in the change from baseline in the number of valid responses from the RVIP.95% CI: [0.3, 5.2]ANCOVA
Comparison: Null hypothesis was no difference in treatments in the change from baseline in the number of valid responses from the RVIP.95% CI: [-1.7, 3.9]ANCOVA
Secondary
Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test
Auditory and visual attention of participants was evaluated using a validated Sustained Attention task. For the sustained auditory attention task, participants were required to respond whenever they heard the number '8' in a continuous stream of numbers presented through headphones. This was identified in the output file by a value of '8' in the 'NUMBER' column. For the sustained visual attention task, participants were required to respond to the letter 's' every time it appeared in a continuous stream of letters presented on a screen. This was identified in the output file by a value of 's' in the 'LETTER' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'.
Time frame: Baseline, 60 minutes and up to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 120 mins | 2.0 Correct responses |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 60 mins | 1.0 Correct responses |
| Paracetamol (1000) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 60 mins | 0.5 Correct responses |
| Paracetamol (1000) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 120 mins | 1.0 Correct responses |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 60 mins | 2.0 Correct responses |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 120 mins | 1.0 Correct responses |
| Paracetamol (500) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 60 mins | 0.0 Correct responses |
| Paracetamol (500) | Change From Baseline in Number of Accurate Responses to Sustained Attention Tasks (SAT) Cognitive Test | Number of Accurate Responses to SAT at 120 mins | 2.0 Correct responses |
Secondary
Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task
The no. of inaccurate responses to RVIP was determined from cognitive function computerised output. Participants monitored a series of single numbers (0-9) appearing in the centre of screen. They responded to consecutive sequences of 3 odd or even numbers by pressing the corresponding response button. This was identified in the output file by a value of '1' in the 'TARGET=1' column. If a subject responded incorrectly to stimuli (pressed the response button at the wrong time), this was identified by a value of '-1' in the 'CORRECT=1' column. The no. of incorrect responses was calculated as the total no. of records where 'CORRECT=1' had a value of '-1'. If the subject missed a target (failed to press the response button within 600 msecs of being presented with a string of 3 consecutive even or odd numbers), this was considered a missed response and was calculated as the no. of records where there was a value of '1' in the 'TARGET=1' column and a value of '0' in the 'CORRECT=1' column.
Time frame: Baseline, 60 minutes and up to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 60 minutes | -5.7 inaccurate and missed responses | Standard Error 3.43 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 120 minutes | -7.6 inaccurate and missed responses | Standard Error 1.14 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 120 minutes | -4.5 inaccurate and missed responses | Standard Error 4.12 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 60 minutes | -8.1 inaccurate and missed responses | Standard Error 1.03 |
| Paracetamol (1000) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 120 minutes | -1.7 inaccurate and missed responses | Standard Error 1.78 |
| Paracetamol (1000) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 60 minutes | -4.8 inaccurate and missed responses | Standard Error 1.18 |
| Paracetamol (1000) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 60 minutes | -2.8 inaccurate and missed responses | Standard Error 1.38 |
| Paracetamol (1000) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 120 minutes | -4.8 inaccurate and missed responses | Standard Error 1.15 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 120 minutes | -6.5 inaccurate and missed responses | Standard Error 0.8 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 60 minutes | 1.4 inaccurate and missed responses | Standard Error 1.96 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 120 minutes | -0.8 inaccurate and missed responses | Standard Error 1.97 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 60 minutes | -4.8 inaccurate and missed responses | Standard Error 0.83 |
| Paracetamol (500) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 60 minutes | -3.1 inaccurate and missed responses | Standard Error 0.89 |
| Paracetamol (500) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 60 minutes | -2.4 inaccurate and missed responses | Standard Error 1.82 |
| Paracetamol (500) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Missed responses at 120 minutes | -3.5 inaccurate and missed responses | Standard Error 0.92 |
| Paracetamol (500) | Change From Baseline in Number of Inaccurate and Missed Responses to RVIP Cognitive Task | Incorrect responses at 120 minutes | -3.3 inaccurate and missed responses | Standard Error 1.56 |
Secondary
Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test
For the Divided Attention task, participants were required to respond on hearing the no. '8' in a continuous stream of numbers through headphones or seeing a letter 's' on screen. This was identified in the output file by a value of '8' in 'NUMBER' column or 's' in 'LETTER' column. If a subject responded incorrectly (pressed the response button at the wrong time), this was identified by a value of '-1' in 'CORRECT=1' column. The number of incorrect responses was calculated as the total no. of records where 'CORRECT=1' had a value of '-1'. If the subject missed a target (failed to press the response button on hearing the no. '8' or seeing the letter 's'), this was considered a missed response. The number of missed responses was calculated as the no. of records where there was a value of '8' in 'NUMBER' column or 's' in 'LETTER' column and a value of '0' in the 'CORRECT=1' column.
Time frame: Baseline, 60 minutes and up to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 60 minutes | -10.2 incorrect and missed responses | Standard Error 1.27 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 120 minutes | -12.2 incorrect and missed responses | Standard Error 1.54 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 120 minutes | -7.1 incorrect and missed responses | Standard Error 1.01 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 60 minutes | -6.5 incorrect and missed responses | Standard Error 1.02 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 60 minutes | -4.2 incorrect and missed responses | Standard Error 1.11 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 120 minutes | -9.1 incorrect and missed responses | Standard Error 2.27 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 120 minutes | -4.9 incorrect and missed responses | Standard Error 1.1 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 60 minutes | -7.6 incorrect and missed responses | Standard Error 2.08 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 120 minutes | -10.2 incorrect and missed responses | Standard Error 1.43 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 120 minutes | -5.6 incorrect and missed responses | Standard Error 0.86 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 60 minutes | -5.4 incorrect and missed responses | Standard Error 0.87 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 60 minutes | -9.8 incorrect and missed responses | Standard Error 1.19 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 60 minutes | -3.3 incorrect and missed responses | Standard Error 0.81 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 120 minutes | -7.8 incorrect and missed responses | Standard Error 1.58 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Incorrect responses at 120 minutes | -5.0 incorrect and missed responses | Standard Error 0.98 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to DAT Cognitive Test | Missed responses at 60 minutes | -6.2 incorrect and missed responses | Standard Error 1.5 |
Secondary
Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test
For sustained auditory attention task, participants were required to respond on hearing the no. '8' in a continuous stream of numbers through headphones. It was identified in output file by a value of '8' in 'NUMBER' column. For sustained visual attention task, participants responded to letter 's' every time it appeared in a continuous stream of letters presented on screen. This was identified in output file by a value of 's' in 'LETTER' column. If a subject responded incorrectly (pressed the response button at the wrong time), it was identified by a value of '-1' in 'CORRECT=1' column. The no. of incorrect responses was calculated as total no. of records where 'CORRECT=1' had a value of '-1'. The no. of missed responses (when subject failed to press the response button on hearing the number '8' or seeing the letter 's'), was calculated as the no. of records where there was a value of '8' in 'NUMBER' column or 's' in the 'LETTER' column and a value of '0' in the 'CORRECT=1' column.
Time frame: Baseline, 60 minutes and up to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 60 minutes | -4.6 incorrect and missed responses | Standard Error 1 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 60 minutes | -2.7 incorrect and missed responses | Standard Error 0.74 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 120 minutes | -2.8 incorrect and missed responses | Standard Error 1.11 |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 120 minutes | -4.4 incorrect and missed responses | Standard Error 1.04 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 60 minutes | -1.9 incorrect and missed responses | Standard Error 1.25 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 120 minutes | -2.0 incorrect and missed responses | Standard Error 1.19 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 60 minutes | -1.1 incorrect and missed responses | Standard Error 0.87 |
| Paracetamol (1000) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 120 minutes | -2.3 incorrect and missed responses | Standard Error 0.98 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 120 minutes | -2.2 incorrect and missed responses | Standard Error 0.64 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 60 minutes | -2.3 incorrect and missed responses | Standard Error 0.7 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 120 minutes | -4.3 incorrect and missed responses | Standard Error 0.88 |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 60 minutes | -4.2 incorrect and missed responses | Standard Error 0.74 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 60 minutes | -1.6 incorrect and missed responses | Standard Error 0.71 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Incorrect responses at 120 minutes | -2.8 incorrect and missed responses | Standard Error 0.82 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 60 minutes | -0.8 incorrect and missed responses | Standard Error 0.66 |
| Paracetamol (500) | Change From Baseline in Number of Incorrect and Missed Responses to SAT Cognitive Test | Missed responses at 120 minutes | -2.4 incorrect and missed responses | Standard Error 0.63 |
Secondary
Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test
Auditory and visual attention of participants was evaluated using a validated Divided Attention task. Participants were required to respond whenever they heard the number '8' in a continuous stream of numbers presented through headphones or saw a letter 's' on the screen . This was identified in the output file by a value of '8' in the 'NUMBER' column or by a value of 's' in the 'LETTER' column. If the subject correctly responded to the target, this was identified by a value of '1' in the 'CORRECT=1' column. The number of accurate responses was calculated as the total number of records where 'CORRECT=1' had a value of '1'.
Time frame: Baseline, 60 minutes and up to 120 minutes post treatment administration
Population: ITT population: all randomized participants who received study treatment and had at least one post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 120 minutes | 11.0 Correct responses |
| Paracetamol + Caffeine Combination (1000/130) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 60 minutes | 10.0 Correct responses |
| Paracetamol (1000) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 60 minutes | 6.0 Correct responses |
| Paracetamol (1000) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 120 minutes | 6.0 Correct responses |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 60 minutes | 8.0 Correct responses |
| Paracetamol + Caffeine Combination (500/65) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 120 minutes | 9.0 Correct responses |
| Paracetamol (500) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 60 minutes | 5.5 Correct responses |
| Paracetamol (500) | Change From Baseline in Number of Valid Responses to Divided Attention Task (DAT) Cognitive Test | 120 minutes | 7.0 Correct responses |