Iota-Carrageenan Nasal Spray in Common Cold

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01944631
• Collaborator: (none)
• Enrollment: 200
• Location: 1
• Arms: 2
• Duration (Months): 5.9
• Patients Per Site Per Month: 33.6

Study Details

Study Description

Brief Summary

The aim of this clinical trial is to investigate the effect of Iota-Carrageenan treatment on cold symptoms. The effect of treatment on the duration of the cold and the patients viral load plus cytokine level indicating the inflammatory response will be analyzed.

Condition or Disease	Intervention/Treatment	Phase
Common Cold	Device: Placebo; Device: Iota-Carrageenan	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Iota-Carrageenan Nasal Spray 1.2 g/l (0.12 Percent) (Bisolviral) Versus Placebo Nasal Spray in the Early Treatment of Common Cold
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Nasal spray 4 times a day over 4 to 10 days	Device: Placebo; Nasal spray saline
Experimental: Iota-Carrageenan nasal spray Nasal spray 4 times a day over 4 to 10 days	Device: Iota-Carrageenan; Nasal spray containing 1.20 g/l Iota-Carrageenan in saline

Outcome Measures

Primary Outcome Measures

1. Total Symptom Score (TSS) Over Days 2 to 4 (TSS2-4) [Days 2, 3 and 4]

   The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean over days 2 to 4 (TSS2-4) was calculated as (TSS2 + TSS3 + TSS4)/3 where TSS2, TSS3 and TSS4 are the total symptom scores calculated for days 2, 3 and 4 respectively. TSS2-4 ranges from 0 (no symptoms) to 24 (severe symptoms).

Secondary Outcome Measures

1. Mean of the Sum of 3 Single Systemic Common Cold Symptom Scores Over Days 2 to 4 (SSS2-4) [Days 2, 3 and 4]

   The mean of the sum of 3 single systemic common cold symptom scores (headache, muscle ache, chilliness). Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 3 single systemic common cold symptom scores over days 2-4 was calculated as (SSS2 + SSS3 + SSS4)/3 where SSS2, SSS3 and SSS4 are the systemic common cold symptom scores calculated for days 2, 3 and 4 respectively. SSS2-4 ranges from 0 (no symptoms) to 9 (severe symptoms).

2. Mean of the Sum of 5 Single Local Common Cold Symptom Scores Mean Over Days 2 to 4 (LSS2-4) [Days 2, 3 and 4]

   The mean of the sum of 5 single local common cold symptom scores (sore throat, blocked nose, runny nose, cough and sneezing). Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 5 single local common cold symptom scores over days 2 to 4 was calculated as (LSS2 + LSS3 + LSS4)/3 where LSS2, LSS3 and LSS4 are the local common cold symptom scores calculated for days 2, 3 and 4 respectively. LSS2-4 ranges from 0 (no symptoms) to 15 (severe symptoms).

3. Area Under the Curve (AUC) Over the 10-day Period for the TSS (AUC-TSS 1-10) [Days 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10]

   The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The Area under the curve (AUC) over the 10-day period for the total symptom score (AUC-TSS 1-10) was calculated as the sum of the TSS calculated on each day from day 1 to day 10. AUC-TSS 1-10 ranges from 0 (no symptoms) to 270 (severe symptoms).

4. Duration of the Cold [Baseline up to 10 days]

   Duration of the common cold was assessed by the question "Do you still have a cold?" at the end of each treatment day. The duration of the cold was defined as ended by the first day of a "No" answer to this daily question.

5. Patient Overall Assessment of Efficacy [Day 10]

   Patient overall assessment of efficacy was assessed by the question "How effective was the treatment in relieving your common cold symptoms?" at day 10. A 5-point scale was used (0=poor, 1=fair, 2=good, 3=very good, 4=excellent).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Patients consider that they are in an early stage of common cold with symptoms of no more than 48 hours duration

• Symptom score of equal or more than 1 for for at least one of the symptoms sore throat, runny nose and blocked nose on a 0-3 verbal rating scale

• Total symptom score of equal or less 9 for symptoms headache, muscle ache, chilliness, sore throat, blocked nose, runny nose, cough, and sneezing measured on a 0-3 verbal rating scale

• Patients agree to refrain from taking any products intended to prevent, intervene in, or treat cough/colds/flu, starting at study entry and continuing through day 10 (e.g. those containing zinc, Echinacea); use of a daily multivitamin is allowed.

Exclusion criteria:

• Known hypersensitivity or are allergic to any component of the test device

• Clinically significant cardiovascular, endocrinological, neurological, respiratory, gastrointestinal disease or history or any current disease that is considered by the investigator as a reason for exclusion e.g. current allergic rhinitis, chronic obstructive pulmonary disease

• Severe nasal septum deviation or other condition that could cause nasal obstruction such as the presence of nasal polyps.

• History of nasal or sinus surgery that in the opinion of the investigator may influence symptom scores

• Taking any prescribed medication other than for contraception, that is considered by the investigator as a reason for exclusion e.g. systemic steroids, intranasal medicines, antibiotics

• Common cold or flu like symptoms for more than 48 hours.

• Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of the investigator may influence symptom scores (analgesics, nasal decongestants, cough medicines)

• Current smoker (more than 10 cigarettes a day)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1326.1.44001 Boehringer Ingelheim Investigational Site	Cardiff		United Kingdom

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01944631
• Other Study ID Numbers: 1326.1
• First Posted: Sep 17, 2013
• Last Update Posted: Apr 3, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Common Cold

Study Results

Participant Flow

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patients received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Period Title: Overall Study
STARTED	100	100
COMPLETED	96	98
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Placebo	Bisolviral	Total
Arm/Group Description	Patients received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Total of all reporting groups
Overall Participants	100	100	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.93 (1.90)	20.01 (2.37)	19.97 (2.14)
Sex: Female, Male (Count of Participants)
Female	62 62%	60 60%	122 61%
Male	38 38%	40 40%	78 39%

Outcome Measures

1. Primary Outcome

Title	Total Symptom Score (TSS) Over Days 2 to 4 (TSS2-4)
Description	The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean over days 2 to 4 (TSS2-4) was calculated as (TSS2 + TSS3 + TSS4)/3 where TSS2, TSS3 and TSS4 are the total symptom scores calculated for days 2, 3 and 4 respectively. TSS2-4 ranges from 0 (no symptoms) to 24 (severe symptoms).
Time Frame	Days 2, 3 and 4

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) which included all randomised patients who used at least one dose of trial treatment, who provided a baseline total symptom score (TSS) as well as any post-treatment data for the primary endpoint.

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Measure Participants	97	98
Least Squares Mean (Standard Error) [units on a scale]	6.390 (0.254)	5.777 (0.253)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bisolviral
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0895
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.613
	Confidence Interval	(2-Sided) 95%; -1.321 to 0.095
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.359
	Estimation Comments	Difference calculated as bisolviral minus placebo

2. Secondary Outcome

Title	Mean of the Sum of 3 Single Systemic Common Cold Symptom Scores Over Days 2 to 4 (SSS2-4)
Description	The mean of the sum of 3 single systemic common cold symptom scores (headache, muscle ache, chilliness). Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 3 single systemic common cold symptom scores over days 2-4 was calculated as (SSS2 + SSS3 + SSS4)/3 where SSS2, SSS3 and SSS4 are the systemic common cold symptom scores calculated for days 2, 3 and 4 respectively. SSS2-4 ranges from 0 (no symptoms) to 9 (severe symptoms).
Time Frame	Days 2, 3 and 4

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Measure Participants	97	98
Least Squares Mean (Standard Error) [units on a scale]	1.297 (0.103)	1.121 (0.103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bisolviral
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2310
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.176
	Confidence Interval	(2-Sided) 95%; -0.464 to 0.113
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.146
	Estimation Comments	Difference calculated as bisolviral minus placebo

3. Secondary Outcome

Title	Mean of the Sum of 5 Single Local Common Cold Symptom Scores Mean Over Days 2 to 4 (LSS2-4)
Description	The mean of the sum of 5 single local common cold symptom scores (sore throat, blocked nose, runny nose, cough and sneezing). Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The mean of the sum of 5 single local common cold symptom scores over days 2 to 4 was calculated as (LSS2 + LSS3 + LSS4)/3 where LSS2, LSS3 and LSS4 are the local common cold symptom scores calculated for days 2, 3 and 4 respectively. LSS2-4 ranges from 0 (no symptoms) to 15 (severe symptoms).
Time Frame	Days 2, 3 and 4

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Measure Participants	97	98
Least Squares Mean (Standard Error) [units on a scale]	5.100 (0.215)	4.657 (0.214)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bisolviral
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1465
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.443
	Confidence Interval	(2-Sided) 95%; -1.042 to 0.156
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.304
	Estimation Comments	Difference calculated as bisolviral minus placebo

4. Secondary Outcome

Title	Area Under the Curve (AUC) Over the 10-day Period for the TSS (AUC-TSS 1-10)
Description	The total symptom score (TSS) is the sum of the 8 single common cold symptom scores consisting of 3 systemic (headache, muscle ache and chilliness) and 5 local (sore throat, blocked nose, runny nose, cough and sneezing) symptoms. Each common cold symptom was scored on a 4-point ordinal scale: 0 = symptom not present 1 = mild symptom (I can feel it but it has not disturbed or irritated me) 2 = moderate symptom (symptom has disturbed and irritated me some of the time) 3 = severe symptom (symptom has disturbed and irritated me most of the time) The Area under the curve (AUC) over the 10-day period for the total symptom score (AUC-TSS 1-10) was calculated as the sum of the TSS calculated on each day from day 1 to day 10. AUC-TSS 1-10 ranges from 0 (no symptoms) to 270 (severe symptoms).
Time Frame	Days 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Measure Participants	97	98
Least Squares Mean (Standard Error) [units on a scale * days]	41.214 (2.199)	41.941 (2.187)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bisolviral
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8148
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.728
	Confidence Interval	(2-Sided) 95%; -5.390 to 6.845
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.102
	Estimation Comments	Difference calculated as bisolviral minus placebo

5. Secondary Outcome

Title	Duration of the Cold
Description	Duration of the common cold was assessed by the question "Do you still have a cold?" at the end of each treatment day. The duration of the cold was defined as ended by the first day of a "No" answer to this daily question.
Time Frame	Baseline up to 10 days

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Measure Participants	97	98
Median (95% Confidence Interval) [days]	7	8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bisolviral
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1887
	Comments
	Method	Log Rank
	Comments	Log-rank test stratifying for the variable 'baseline TSS'

6. Secondary Outcome

Title	Patient Overall Assessment of Efficacy
Description	Patient overall assessment of efficacy was assessed by the question "How effective was the treatment in relieving your common cold symptoms?" at day 10. A 5-point scale was used (0=poor, 1=fair, 2=good, 3=very good, 4=excellent).
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.	Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
Measure Participants	97	98
Excellent	2.1 2.1%	2.0 2%
Very good	11.3 11.3%	16.3 16.3%
Good	36.1 36.1%	33.7 33.7%
Fair	33.0 33%	28.6 28.6%
Poor	17.5 17.5%	19.4 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bisolviral
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6954
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.1069
	Confidence Interval	(2-Sided) 95%; 0.666 to 1.840
	Parameter Dispersion	Type: Value:
	Estimation Comments	A value greater than one favours bisolviral

Adverse Events

Time Frame	From first nasal spray administration until the application discontinuation date plus one day, up to 11 days
Arm/Group Title	Placebo		Bisolviral
Arm/Group Description	Patient received an application of placebo nasal spray saline 4 times a day, for 4 to 10 days. One application means one puff into each nostril.		Patients received an application of 1.20g/l Iota-Carrageenan in saline nasal spray 4 times a day, for 4 to 10 days. One application means one puff into each nostril.
All Cause Mortality
	Placebo		Bisolviral
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Bisolviral
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Bisolviral
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/100 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.