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Double-blind Trial to Investigate Efficacy and Tolerance of Ambroxol Lozenges 20 mg in Sore Throat

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ClinicalTrials.gov Identifier: NCT00525044
Recruitment Status : Completed
First Posted : September 5, 2007
Results First Posted : July 11, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Pharyngitis
Interventions Drug: Ambroxol
Drug: Placebo
Enrollment 249
Recruitment Details Male or female outpatients, 18 to 65 years of age, suffering from acute viral pharyngitis and throat pain of at least severe intensity were to enter the trial.
Pre-assignment Details Double-blind, randomized, placebo-controlled parallel design in comparison of two arms
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description Patients were orally administered Ambroxol lozenges 20 milligram (mg) initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
Period Title: Overall Study
Started 124 125
Completed 124 124
Not Completed 0 1
Reason Not Completed
Lost to Follow-up             0             1
Arm/Group Title Ambroxol Lozenges 20 mg Placebo Total
Hide Arm/Group Description Patients were orally administered Ambroxol lozenges 20 milligram (mg) initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days. Total of all reporting groups
Overall Number of Baseline Participants 124 125 249
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): FAS, which included all patients who were randomized, who took at least the first lozenge, who had Pain Intensity (PI) data of baseline.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 125 participants 249 participants
36.0  (12.2) 38.4  (13.0) 37.2  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 125 participants 249 participants
Female
67
  54.0%
71
  56.8%
138
  55.4%
Male
57
  46.0%
54
  43.2%
111
  44.6%
1.Primary Outcome
Title Sum of Pain Intensity Difference (SPIDnorm)-Time-weighted Average of the Pain Intensity Difference (PID) From Pre-dose Baseline Over the First 3 Hours After the First Lozenge Expressed as a Ratio of the Pre-dose Baseline
Hide Description The calculation will be based on the pain intensity (PI) assessment by the patient before and then at (pain intensity difference at 30 minutes (PID30)), (pain intensity difference at 60 minutes (PID60)), (pain intensity difference at 120 minutes (PID120)) and (pain intensity difference at 180 minutes (PID180)) after the 1st lozenge. Using the difference in PI from pre-dose baseline for each time point subsequent to dosing, the SPIDnorm will be calculated as SPIDnorm = (30*PID30 + 30*PID60 + 60*PID120 + 60*PID180)/(180*PI (baseline)) The patient rates the intensity of his sore throat pain on a 6-point Verbal Rating Scale (VRS) pain intensity (PI) before taking the first lozenge and 30, 60, 120 and 180 minutes thereafter, and enters his rating in his patient's diary . The rating scale is as follows: 0=no pain; 1=hardly any pain; 2=slight pain; 3=moderate pain; 4=severe pain; 5=very severe pain.
Time Frame pre-dose baseline and 30, 60, 120, and 180 minutes
Hide Outcome Measure Data
Hide Analysis Population Description

Full Analysis Set (FAS): FAS, which included all patients

  • who were randomized,
  • who took at least the first lozenge,
  • who had PI data of baseline.
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description:
Patients were orally administered Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day
Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
Overall Number of Participants Analyzed 124 125
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.40  (0.020) -0.34  (0.020)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Differences between the treatment groups with regard to the primary endpoint SPIDnorm was tested using an analysis of variance (ANOVA) including treatment and centre as fix effects.

Treatment differences were estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0156
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.12 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.028
Estimation Comments Treatment differences (Ambroxol- Placebo)
2.Secondary Outcome
Title Pain Intensity (PI) as Rated on a 6-point VRS by the Patient at 0.5, 1, 2 and 3 Hours After the First Lozenge
Hide Description

Pain intensity (PI) as rated on a 6-point Verbal Rating Scale (VRS) by the patient at 0.5, 1, 2 and 3 hours after the first lozenge.

The patient rates the intensity of his sore throat condition on a 6-point rating scale [VRS(PI)-verbal rating scale (pain intensity)] before taking the first lozenge and 30, 60, 120 and 180 minutes thereafter, and enters his rating in his patient's diary . The rating scale is as follows: 0=no pain; 1=hardly any pain; 2=slight pain; 3=moderate pain; 4=severe pain; 5=very severe pain.

Adjusted Mean (Standard Error) are presented for this outcome measure.

Time Frame 0.5, 1, 2 and 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description:
Patients were orally administered Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day
Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
Overall Number of Participants Analyzed 124 125
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
30 minutes 2.9  (0.08) 3.1  (0.07)
60 minutes 2.6  (0.08) 2.8  (0.08)
120 minutes 2.3  (0.10) 2.7  (0.09)
180 minutes 2.2  (0.10) 2.5  (0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 30 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1280
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments Treatment differences (Ambroxol- Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 60 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0417
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments Treatment differences (Ambroxol- Placebo)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 120 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.6 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments Treatment differences (Ambroxol- Placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 180 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0201
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.6 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments Treatment differences (Ambroxol- Placebo
3.Secondary Outcome
Title Pain Intensity Difference From Pre-dose Baseline (PID) as Rated on a 6-point Verbal Rating Scale (VRS) by the Patient at 0.5, 1, 2 and 3 Hours After the First Lozenge
Hide Description

Pain intensity difference from pre-dose baseline (PID) as rated on a 6-point Verbal Rating Scale (VRS) by the patient at 0.5, 1, 2 and 3 hours after the first lozenge.

Adjusted Mean (Standard Error) are presented for this outcome measure.

Time Frame pre-dose baseline and 0.5, 1, 2 and 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description:
Patients were orally administered Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day
Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
Overall Number of Participants Analyzed 124 125
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
30 minutes -1.1  (0.08) -1.0  (0.07)
60 minutes -1.4  (0.08) -1.2  (0.08)
120 minutes -1.8  (0.10) -1.4  (0.09)
180 minutes -1.9  (0.10) -1.6  (0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 30 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1280
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments Treatment differences (Ambroxol- Placebo)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 60 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0417
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments Treatment differences (Ambroxol- Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 120 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.6 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments Treatment differences (Ambroxol- Placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at 180 min:

analysis of covariance (ANCOVA) including treatment and centre as fix effects and baseline as covariable are presented. Treatment differences are estimated by reference to the adjusted least squares mean differences and the corresponding 95 % confidence intervals.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0201
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.6 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments Treatment differences (Ambroxol- Placebo
4.Secondary Outcome
Title Assessment of Redness of the Pharyngeal Mucosa by the Investigator on a 5-point VRS at Pre-dose Baseline and at the End-of-study Evaluation
Hide Description Assessment of redness of the pharyngeal mucosa by the investigator on a 5-point VRS (normal, slightly red, clearly red, very red, severe inflammation) at pre-dose baseline and at the end-of-study evaluation.
Time Frame Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description

SAFETY Set, which included all patients

  • who were randomized,
  • who took at least one dose of trial medication.
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description:
Patients were orally administered Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day
Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
Overall Number of Participants Analyzed 124 125
Measure Type: Number
Unit of Measure: percentage of participants
Day 1_Normal Number Analyzed 124 participants 125 participants
0.0 0.8
Day 1_Slightly red Number Analyzed 124 participants 125 participants
12.1 12.8
Day 1_ Clearly red Number Analyzed 124 participants 125 participants
53.2 50.4
Day 1_Very red Number Analyzed 124 participants 125 participants
29.8 32.0
Day 1_Severe inflammation Number Analyzed 124 participants 125 participants
4.8 4.0
Day 2_Normal Number Analyzed 124 participants 124 participants
12.1 10.5
Day 2_Slightly red Number Analyzed 124 participants 124 participants
66.9 66.9
Day 2_Clearly red Number Analyzed 124 participants 124 participants
18.5 21.8
Day 2_Very red Number Analyzed 124 participants 124 participants
2.4 0.8
Day 2_Severe inflammation Number Analyzed 124 participants 124 participants
0.0 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at day 1:

P-value was calculated by the Cochran-Mantel-Haenszel test adjusting for center.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9939
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at day 2:

P-value was calculated by the Cochran-Mantel-Haenszel test adjusting for center.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5552
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Assessment of Patients' Assessment of Effectiveness on a 5-point VRS at Pre-dose Baseline and at the End-of-study Evaluation
Hide Description Assessment of Patients' Assessment of Effectiveness on a 5-point VRS ("very good", "good", "neither good nor poor", "not very good", "not at all good") at pre-dose baseline and at the end-of-study evaluation
Time Frame Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description:
Patients were orally administered Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day
Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
Overall Number of Participants Analyzed 124 125
Measure Type: Number
Unit of Measure: percentage of participants
Day 1_Very good Number Analyzed 124 participants 125 participants
13.7 8.0
Day 1_Good Number Analyzed 124 participants 125 participants
58.1 52.0
Day 1_Neither good nor poor Number Analyzed 124 participants 125 participants
19.4 18.4
Day 1_Not very good Number Analyzed 124 participants 125 participants
6.5 16.0
Day 1_Not at all good Number Analyzed 124 participants 125 participants
2.4 5.6
Day 2_Very good Number Analyzed 111 participants 113 participants
24.3 14.2
Day 2_Good Number Analyzed 111 participants 113 participants
56.8 52.2
Day 2_Neither good nor poor Number Analyzed 111 participants 113 participants
14.4 16.8
Day 2_Not very good Number Analyzed 111 participants 113 participants
3.6 13.3
Day 2_Not at all good Number Analyzed 111 participants 113 participants
0.9 3.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at day 1:

P-value was calculated by the Cochran-Mantel-Haenszel test adjusting for center.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0343
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ambroxol Lozenges 20 mg, Placebo
Comments

Analysis at day 2:

P-value was calculated by the Cochran-Mantel-Haenszel test adjusting for center.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0119
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Time Frame From drug administration until end of the treatment, up to 2 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ambroxol Lozenges 20 mg Placebo
Hide Arm/Group Description Patients were orally administered Ambroxol lozenges 20 milligram (mg) initially (first lozenges); up to 6 lozenges per day up to two days, maximal dose:120 mg per day Patients were orally administered Placebo matching Ambroxol lozenges 20 mg initially (first lozenges); up to 6 lozenges per day up to two days.
All-Cause Mortality
Ambroxol Lozenges 20 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/124 (0.00%)   0/125 (0.00%) 
Hide Serious Adverse Events
Ambroxol Lozenges 20 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/124 (0.00%)   0/125 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ambroxol Lozenges 20 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/124 (0.00%)   0/125 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00525044    
Other Study ID Numbers: 18.490
First Submitted: September 3, 2007
First Posted: September 5, 2007
Results First Submitted: December 20, 2018
Results First Posted: July 11, 2019
Last Update Posted: July 11, 2019