Trial Outcomes & Findings for A Comparison of Solid and Soluble Forms of Cold and Influenza Remedies (NCT NCT01332578)

NCT ID: NCT01332578

Last Updated: 2015-06-01

Results Overview

Time to reach plasma paracetamol concentration of 0.25 μg/mL was determined using plasma concentration time profiles.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 25 participants
• Primary outcome timeframe: 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
• Results posted on: 2015-06-01

Participant Flow

Participants were recruited at one clinical study site in Glasgow.

Of 37 participants screened, 12 participants did not meet the study criteria. Remaining 25 participants were randomized into the study.

Participant milestones

Measure	Hot Drink Remedy First, Then Standard Paracetamol Tablets Participants received one sachet of hot drink remedy containing 1000 milligram (mg) paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid in 150 milliliter (mL) of radio-labeled water (first intervention period). After a washout period of minimum two days, a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL water were administered (second intervention period).	Standard Paracetamol Tablets First, Then Hot Drink Remedy Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water (first intervention period). After a washout period of minimum two days, one sachet of hot drink remedy with 150 mL of radio-labeled water was administered (second intervention period).
Period I STARTED	12	13
Period I COMPLETED	12	13
Period I NOT COMPLETED	0	0
Washout Period STARTED	12	13
Washout Period COMPLETED	12	13
Washout Period NOT COMPLETED	0	0
Period II STARTED	12	13
Period II COMPLETED	12	13
Period II NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Comparison of Solid and Soluble Forms of Cold and Influenza Remedies

Baseline characteristics by cohort

Measure	All Randomized Participants n=25 Participants All randomized participants who received a study treatment during the cross over study.
Age, Continuous	30.5 Years STANDARD_DEVIATION 11.23 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Time to reach plasma paracetamol concentration of 0.25 μg/mL was determined using plasma concentration time profiles.

Outcome measures

Measure	Hot Drink Remedy n=24 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=25 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Time to Reach Plasma Paracetamol Concentration of 0.25 μg/mL (Microgram Per Milliliter)	4.59 minutes Interval 3.4 to 11.1	23.14 minutes Interval 6.0 to 46.6

SECONDARY outcome

Timeframe: 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.

AUC (0-30 min) was determined from paracetamol plasma concentration time profiles using trapezoidal rule.

Outcome measures

Measure	Hot Drink Remedy n=24 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=6 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
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 873.300	387.28 nanograms (ng)*hours (h)/mL Standard Deviation 363.139

SECONDARY outcome

Timeframe: 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.

AUC (0-60 min) was determined from paracetamol plasma concentration time profiles using trapezoidal method.

Outcome measures

Measure	Hot Drink Remedy n=24 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=20 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
AUC (0-60 Min)	5007.11 ng*h/mL Standard Deviation 1890.135	1874.22 ng*h/mL Standard Deviation 1555.539

SECONDARY outcome

Timeframe: 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.

Cmax was determined using plasma paracetamol concentration time profile.

Outcome measures

Measure	Hot Drink Remedy n=24 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=25 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Maximum Plasma Concentration (Cmax)	8309.58 ng/mL Standard Deviation 2109.196	9225.20 ng/mL Standard Deviation 1681.200

SECONDARY outcome

Timeframe: 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.

Time after administration when the maximum plasma concentration was reached.

Outcome measures

Measure	Hot Drink Remedy n=24 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=25 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Time to Maximum Plasma Concentration (Tmax)	1.50 hours Interval 0.2 to 2.0	1.99 hours Interval 0.7 to 3.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Hot Drink Remedy n=11 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=13 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Time to Onset of Gastric Emptying	7.86 minutes Standard Error 3.909	54.23 minutes Standard Error 3.596

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Hot Drink Remedy n=11 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=13 Participants Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Time to Completion of Gastric Emptying	202.59 minutes Standard Error 16.811	168.38 minutes Standard Error 15.463

SECONDARY outcome

Timeframe: 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.

Qualitative onset and completion of tablet disintegration was determined using Gamma scintigraphy images and WebLink image analysis program.

Outcome measures

Measure	Hot Drink Remedy n=13 Participants Participants received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Time to Onset and Completion of Disintegration of Reference Tablets Onset Time of Disintegration	42.50 minutes Standard Deviation 18.028 • Interval 12.5 to 67.5	—
Time to Onset and Completion of Disintegration of Reference Tablets Completion Time of Disintegration	62.88 minutes Standard Deviation 24.788 • Interval 22.5 to 112.5	—

Adverse Events

Hot Drink Remedy

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Standard Paracetamol Tablets

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Hot Drink Remedy n=25 participants at risk Participants then received one sachet of hot drink remedy powder containing 1000 mg paracetamol, 10 mg phenylephrine and 40 mg ascorbic acid, which was dissolved in 150 mL of radio-labeled water.	Standard Paracetamol Tablets n=25 participants at risk Participants received a single dose of two radio-labeled tablets of standard paracetamol (500 mg each) with 150 mL of water.
Investigations Alanine Aminotransferase Increased	0.00% 0/25 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.	4.0% 1/25 • Number of events 1 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.
Investigations Blood Bilirubin Increased	0.00% 0/25 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.	4.0% 1/25 • Number of events 1 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.
Renal and urinary disorders Hematuria	8.0% 2/25 • Number of events 2 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.	0.00% 0/25 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.
Eye disorders Blepharospasm	4.0% 1/25 • Number of events 1 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.	0.00% 0/25 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.
Nervous system disorders Headache	0.00% 0/25 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.	4.0% 1/25 • Number of events 1 • Adverse events were collected from the start of the treatment, and until 5 days following administration of the last dose of investigational product.

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