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Efficacy of Buscopan® in Comparison With 654-II (Anisodamine) in Acute Gastric or Intestinal Pain

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ClinicalTrials.gov Identifier: NCT01929044
Recruitment Status : Completed
First Posted : August 27, 2013
Results First Posted : March 8, 2016
Last Update Posted : March 8, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Intestinal Diseases
Interventions Drug: 654-II (anisodamine)
Drug: Buscopan® (hyoscine butylbromide)
Enrollment 299
Recruitment Details 299 patients were entered and 295 were treated.
Pre-assignment Details  
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Period Title: Overall Study
Started 153 146
Completed 142 129
Not Completed 11 17
Reason Not Completed
Adverse Event             1             0
Protocol Violation             9             14
Not Treated             1             3
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine) Total
Hide Arm/Group Description Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients Total of all reporting groups
Overall Number of Baseline Participants 153 142 295
Hide Baseline Analysis Population Description
Treated Set (TS): All randomised patients who received at least one dose of study medication constituted the treated set. One patient was randomized to 654-II but incorrectly treated with Buscopan® so in the disposition table and efficacy analysis, number of patients are 152 and 143 while for demographic and AE analysis, they are 153 and 142.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 153 participants 142 participants 295 participants
41.5  (14.2) 40.7  (14.8) 41.1  (14.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 142 participants 295 participants
Female
90
  58.8%
76
  53.5%
166
  56.3%
Male
63
  41.2%
66
  46.5%
129
  43.7%
1.Primary Outcome
Title PID From Pre-dose Baseline at 20 Minutes After First Injection.
Hide Description Pain intensity difference (PID) from pre-dose baseline at 20 minutes after first injection. It was assessed using an 11-point numerical rating scale (NRS) ranging from 0 = 'no pain' to 10 = 'worst pain possible'.
Time Frame Baseline and 20 minutes after the first injection
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS: all patients who provided any data for the primary efficacy endpoint constituted the full analysis set.), who revealed no important protocol violations that would impact the analysis of primary endpoint
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-4.09  (0.17) -3.66  (0.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments Restricted maximum likelihood (REML) -repeated measures approach
Type of Statistical Test Non-Inferiority or Equivalence
Comments One-sided test relative to the non-inferiority margin of 1
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Kenward-Roger approximation is used to estimate the denominator degrees of freedom. An unstructured covariance matrix is used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.88 to 0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.23
Estimation Comments REML-based repeated measures approach includes baseline pain intensity as continuous covariate, treatment, centre, time and treatment-time interaction as fixed effects. The difference was calculated as Buscopan minus 654-II.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0743
Comments [Not Specified]
Method Mixed Models Analysis
Comments Kenward-Roger approximation is used to estimate the denominator degrees of freedom. An unstructured covariance matrix is used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.88 to 0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.23
Estimation Comments REML-based repeated measures approach includes baseline pain intensity as continuous covariate, treatment, centre, time and treatment-time interaction as fixed effects. The difference was calculated as Buscopan minus 654-II.
2.Secondary Outcome
Title PID From Pre-dose Baseline at 10 Minutes After First Injection.
Hide Description Pain intensity difference (PID) from pre-dose baseline at 10 minutes after first injection. It was assessed using an 11-point numerical rating scale (NRS) ranging from 0 = 'no pain' to 10 = 'worst pain possible'.
Time Frame Baseline and 10 minutes after the first injection
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS), who revealed no important protocol violations that would impact the analysis of primary endpoint.
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-2.64  (0.14) -2.33  (0.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1210
Comments [Not Specified]
Method Mixed Models Analysis
Comments Kenward-Roger approximation is used to estimate the denominator degrees of freedom. An unstructured covariance matrix is used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.70 to 0.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments REML-based repeated measures approach includes baseline pain intensity as continuous covariate, treatment, centre, time and treatment-time interaction as fixed effects. The difference was calculated as Buscopan minus 654-II.
3.Secondary Outcome
Title PID From Pre-dose Baseline at 30 Minutes After First Injection.
Hide Description Pain intensity difference (PID) from pre-dose baseline at 30 minutes after first injection. It was assessed using an 11-point numerical rating scale (NRS) ranging from 0 = 'no pain' to 10 = 'worst pain possible'.
Time Frame Baseline and 30 minutes after the first injection
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS), who revealed no important protocol violations that would impact the analysis of primary endpoint.
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-5.14  (0.15) -4.74  (0.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0658
Comments [Not Specified]
Method Mixed Models Analysis
Comments Kenward-Roger approximation is used to estimate the denominator degrees of freedom. An unstructured covariance matrix is used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.82 to 0.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.21
Estimation Comments REML-based repeated measures approach includes baseline pain intensity as continuous covariate, treatment, centre, time and treatment-time interaction as fixed effects. The difference was calculated as Buscopan minus 654-II.
4.Secondary Outcome
Title PID From Pre-dose Baseline at 60 Minutes After First Injection.
Hide Description Pain intensity difference (PID) from pre-dose baseline at 60 minutes after first injection. It was assessed using an 11-point numerical rating scale (NRS) ranging from 0 = 'no pain' to 10 = 'worst pain possible'.
Time Frame Baseline and 60 minutes after the first injection
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS), who revealed no important protocol violations that would impact the analysis of primary endpoint.
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-5.96  (0.14) -5.51  (0.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0220
Comments [Not Specified]
Method Mixed Models Analysis
Comments Kenward-Roger approximation is used to estimate the denominator degrees of freedom. An unstructured covariance matrix is used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.85 to -0.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments REML-based repeated measures approach includes baseline pain intensity as continuous covariate, treatment, centre, time and treatment-time interaction as fixed effects. The difference was calculated as Buscopan minus 654-II.
5.Secondary Outcome
Title PID From Pre-dose Baseline at 120 Minutes After First Injection.
Hide Description Pain intensity difference (PID) from pre-dose baseline at 120 minutes after first injection. It was assessed using an 11-point numerical rating scale (NRS) ranging from 0 = 'no pain' to 10 = 'worst pain possible'.
Time Frame Baseline and 120 minutes after the first injection
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS), who revealed no important protocol violations that would impact the analysis of primary endpoint.
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-6.46  (0.13) -6.01  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0149
Comments [Not Specified]
Method Mixed Models Analysis
Comments Kenward-Roger approximation is used to estimate the denominator degrees of freedom. An unstructured covariance matrix is used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.81 to -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.18
Estimation Comments REML-based repeated measures approach includes baseline pain intensity as continuous covariate, treatment, centre, time and treatment-time interaction as fixed effects. The difference was calculated as Buscopan minus 654-II.
6.Secondary Outcome
Title Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection
Hide Description Global assessment of efficacy by the patient. The patient was to assess the efficacy at 120 min after the first injection using a 4-point rating scale by answering the question: "How would you rate the effect of the study medication for relieving your acute gastric or intestinal spasm-like pain?" (0 = poor; 1 = fair; 2 = good; 3 = very good).
Time Frame 120 minutes after the first injection
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS), who revealed no important protocol violations that would impact the analysis of primary endpoint.
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Measure Type: Number
Unit of Measure: Percentage of Patients
Very Good 22.5 22.0
Good 59.2 44.1
Fair 18.3 29.1
Poor 0.0 4.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0113
Comments [Not Specified]
Method van Elteren test
Comments The van Elteren test stratifying for centre (Cochran-Mantel-Haenszel test using modified ridit scores) was performed.
7.Secondary Outcome
Title Proportion of Patients Who Need the Second Injection
Hide Description Proportion of patients who need the second injection at 20 minutes after the first injection.
Time Frame 20 minutes after the first injection.
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS): All patients in full analysis set (FAS), who revealed no important protocol violations that would impact the analysis of primary endpoint.
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description:
Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients
Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
Overall Number of Participants Analyzed 142 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Patients
24.6
(17.81 to 32.58)
33.9
(25.70 to 42.79)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buscopan® (Hyoscine Butylbromide), 654-II (Anisodamine)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0992
Comments [Not Specified]
Method Regression, Logistic
Comments A logistic regression model was used to evaluate the response with treatment as fixed effect and baseline pain intensity as continuous covariate.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.37 to 1.09
Estimation Comments Exact 95% confidence interval obtained by Clopper and Pearson approach.
Time Frame From first study drug application until 2 days (inclusive) after the last study drug application
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Hide Arm/Group Description Single intramuscular injection of 20 mg Buscopan® solution (if needed, second injection with 20 mg was to be made at 20 min after the first one) was administered to the patients Single intramuscular injection of 10 mg Anisodamine solution (if needed, second injection with 10 mg was to be made at 20 min after the first one) was administered to the patients
All-Cause Mortality
Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/153 (0.65%)   0/142 (0.00%) 
Gastrointestinal disorders     
Hernial eventration  1  1/153 (0.65%)  0/142 (0.00%) 
Ileus  1  1/153 (0.65%)  0/142 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Buscopan® (Hyoscine Butylbromide) 654-II (Anisodamine)
Affected / at Risk (%) Affected / at Risk (%)
Total   12/153 (7.84%)   10/142 (7.04%) 
General disorders     
Thirst  1  12/153 (7.84%)  10/142 (7.04%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
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: NCT01929044    
Other Study ID Numbers: 202.848
First Submitted: August 22, 2013
First Posted: August 27, 2013
Results First Submitted: February 10, 2016
Results First Posted: March 8, 2016
Last Update Posted: March 8, 2016