Common Cold, Influenza
Conditions
Brief summary
The study is designed to investigate whether paracetamol from a hot remedy reaches the plasma faster than standard paracetamol tablets. The study will also assess the gastrointestinal transit of two oral cold and influenza ('flu') formulations using gamma scintigraphy. It is postulated that paracetamol in solution, such as from cold and 'flu' hot remedies, provides a greater early exposure compared to standard paracetamol tablets. In addition, the pharmacokinetic (PK) profile of paracetamol in the two formulations will be investigated.
Interventions
DRUGParacetamol
Present in both test and active comparator
DRUGPhenylephrine
Test product
DRUGAscorbic Acid
Test product
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy male volunteers * Body mass index between 18.0-29.9 kg/m\^2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Plasma Paracetamol Concentration of 0.25 μg/mL (Microgram Per Milliliter) | Blood samples taken within 15-30 minutes prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose | Time to reach plasma paracetamol concentration of 0.25 μg/mL was determined using plasma concentration time profiles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-60 Min) | Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose | AUC (0-60 min) was determined from paracetamol plasma concentration time profiles using trapezoidal method. |
| Maximum Plasma Concentration (Cmax) | Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose | Cmax was determined using plasma paracetamol concentration time profile. |
| Time to Maximum Plasma Concentration (Tmax) | Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose | Time after administration when the maximum plasma concentration was reached. |
| Area Under the Concentration/Time Curve From 0 to 30 Minutes (Min) (AUC 0-30 Min) | Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose | AUC (0-30 min) was determined from paracetamol plasma concentration time profiles using trapezoidal rule. |
| Time to Completion of Gastric Emptying | Baseline to 10 hours | Time to completion of gastric emptying of hot drink remedy and standard paracetamol tablets was assessed using Gamma Scintigraphy images and WebLink image analysis program. Completion of gastric emptying was confirmed by two consecutive images with negligible gastric activity. |
| Time to Onset and Completion of Disintegration of Reference Tablets | Baseline to 10 hours post dose | Qualitative onset and completion of tablet disintegration was determined using Gamma scintigraphy images and WebLink image analysis program. |
| Time to Onset of Gastric Emptying | Baseline to 10 hours | The individual anterior and posterior images were assessed using Gamma Scintigraphy images and WebLink Image Analysis program to determine the time to onset of gastric emptying of hot drink remedy and standard paracetamol tablets. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited at one clinical study site in Glasgow.
Pre-assignment details
Of 37 participants screened, 12 participants did not meet the study criteria. Remaining 25 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants who received a study treatment during the cross over study. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 30.5 Years STANDARD_DEVIATION 11.23 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 25 | 3 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Time to Reach Plasma Paracetamol Concentration of 0.25 μg/mL (Microgram Per Milliliter)
Time to reach plasma paracetamol concentration of 0.25 μg/mL was determined using plasma concentration time profiles.
Time frame: Blood samples taken within 15-30 minutes prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose
Population: Modified Intent-To-Treat (MITT) population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in at least one of the two study periods.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hot Drink Remedy | Time to Reach Plasma Paracetamol Concentration of 0.25 μg/mL (Microgram Per Milliliter) | 4.59 minutes |
| Standard Paracetamol Tablets | Time to Reach Plasma Paracetamol Concentration of 0.25 μg/mL (Microgram Per Milliliter) | 23.14 minutes |
Comparison: Null hypothesis was no difference between test hot drink and standard paracetamol tablets.p-value: 0.000495% CI: [-27.31, -15.81]Wilcoxon (Mann-Whitney)
Secondary
Area Under the Concentration/Time Curve From 0 to 30 Minutes (Min) (AUC 0-30 Min)
AUC (0-30 min) was determined from paracetamol plasma concentration time profiles using trapezoidal rule.
Time frame: Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose
Population: MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in at least one of the two study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot Drink Remedy | Area Under the Concentration/Time Curve From 0 to 30 Minutes (Min) (AUC 0-30 Min) | 1535.80 nanograms (ng)*hours (h)/mL | Standard Deviation 873.3 |
| Standard Paracetamol Tablets | Area Under the Concentration/Time Curve From 0 to 30 Minutes (Min) (AUC 0-30 Min) | 387.28 nanograms (ng)*hours (h)/mL | Standard Deviation 363.139 |
Secondary
AUC (0-60 Min)
AUC (0-60 min) was determined from paracetamol plasma concentration time profiles using trapezoidal method.
Time frame: Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose
Population: MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in at least one of the two study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot Drink Remedy | AUC (0-60 Min) | 5007.11 ng*h/mL | Standard Deviation 1890.135 |
| Standard Paracetamol Tablets | AUC (0-60 Min) | 1874.22 ng*h/mL | Standard Deviation 1555.539 |
Secondary
Maximum Plasma Concentration (Cmax)
Cmax was determined using plasma paracetamol concentration time profile.
Time frame: Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose
Population: MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in at least one of the two study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot Drink Remedy | Maximum Plasma Concentration (Cmax) | 8309.58 ng/mL | Standard Deviation 2109.196 |
| Standard Paracetamol Tablets | Maximum Plasma Concentration (Cmax) | 9225.20 ng/mL | Standard Deviation 1681.2 |
Secondary
Time to Completion of Gastric Emptying
Time to completion of gastric emptying of hot drink remedy and standard paracetamol tablets was assessed using Gamma Scintigraphy images and WebLink image analysis program. Completion of gastric emptying was confirmed by two consecutive images with negligible gastric activity.
Time frame: Baseline to 10 hours
Population: Period Level MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in one of the two study periods. Gastric emptying endpoints were only measured in the first period for each participant.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Hot Drink Remedy | Time to Completion of Gastric Emptying | 202.59 minutes | Standard Error 16.811 |
| Standard Paracetamol Tablets | Time to Completion of Gastric Emptying | 168.38 minutes | Standard Error 15.463 |
Secondary
Time to Maximum Plasma Concentration (Tmax)
Time after administration when the maximum plasma concentration was reached.
Time frame: Blood samples taken within 15-30 min prior to dosing and at 3, 5, 7, 9, 11, 15, 20, 30, 45, 90, 120 and 180 minutes post-dose
Population: MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in at least one of the two study periods.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hot Drink Remedy | Time to Maximum Plasma Concentration (Tmax) | 1.50 hours |
| Standard Paracetamol Tablets | Time to Maximum Plasma Concentration (Tmax) | 1.99 hours |
Secondary
Time to Onset and Completion of Disintegration of Reference Tablets
Qualitative onset and completion of tablet disintegration was determined using Gamma scintigraphy images and WebLink image analysis program.
Time frame: Baseline to 10 hours post dose
Population: Period Level MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in one of the two study periods. Tablet Disintegration endpoints were only measured in the first period for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hot Drink Remedy | Time to Onset and Completion of Disintegration of Reference Tablets | Completion Time of Disintegration | 62.88 minutes | Standard Deviation 24.788 |
| Hot Drink Remedy | Time to Onset and Completion of Disintegration of Reference Tablets | Onset Time of Disintegration | 42.50 minutes | Standard Deviation 18.028 |
Secondary
Time to Onset of Gastric Emptying
The individual anterior and posterior images were assessed using Gamma Scintigraphy images and WebLink Image Analysis program to determine the time to onset of gastric emptying of hot drink remedy and standard paracetamol tablets.
Time frame: Baseline to 10 hours
Population: Period Level MITT population: all randomized participants with any post baseline pharmacokinetic measurement or scintigraphic measurement, and had evaluable data in one of the two study periods. Gastric emptying endpoints were only measured in the first period for each participant.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Hot Drink Remedy | Time to Onset of Gastric Emptying | 7.86 minutes | Standard Error 3.909 |
| Standard Paracetamol Tablets | Time to Onset of Gastric Emptying | 54.23 minutes | Standard Error 3.596 |