Intestinal Diseases
Conditions
Brief summary
The aim of the study is to assess the efficacy of Buscopan® (hyoscine butylbromide) in comparison to 654-II (anisodamine)in acute gastric or intestinal spasm-like pain.
Interventions
DRUG654-II (anisodamine)
10mg injection
DRUGBuscopan® (hyoscine butylbromide)
20mg injection
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) guidelines and local regulation prior to participation in the trial. 2. Patients must agree to cooperate with all trial evaluations and perform all required tasks. 3. Patients with acute gastric or intestinal spasm-like pain (without severe vomiting and surgical acute abdomen). 4. Male or female patients aged 18 to 70 years. 5. The pain intensity upon screening is at least point 6 on a 0-10 numerical rating scale (NRS).
Exclusion criteria
1. Patients with the following concomitant disease is not eligible for enrollment: * Painful gastric or intestinal spasm of organic origin such as Crohn's disease, ulcerative colitis, lactose intolerance, gastrointestinal perforation, suspected gastrointestinal perforation or peritoneal effusion. * Pain related with malignancy. * Patients with other severe pain states of organic origin. * Mechanical stenosis of the gastrointestinal tract ,megacolin. * Urinary retention associated with mechanical stenosis of urinary tract. * Narrow-angled glaucoma. * Tachyarrhythmia. * Myasthenia gravis. * Meulengracht-Gilbert syndrome. * Known depression or known mental illness, anxiety disturbance. 2. Patients taking the following concomitant medication within 7 half-life of concomitant medication (the duration from taking concomitant medication to attending the trial is less than 7 half-life) are not eligible for enrollment: * Analgesics, * Spasmolytics, * Anticholinergics * Affecting gastrointestinal motility, such as propantheline, metoclopramide, cisapride, loperamide, diphenoxylate, opioid analgesics, antacids and other ulcer treatment * Regular administration of laxatives * Narcotics * Antidepressant treatment or treatment with psychoactive drugs 3. Pregnancy and/or lactation or planned pregnancy; 4. Known hypersensitivity to N-butylscopolammonium bromide 5. Alcohol, or drug abuse. 6. Simultaneous participating in another clinical trial, or discontinuing from another clinical trial before randomization (administration of study medication); moreover, in the case of screening failure or premature discontinuing from the trial, repeated enrollment is forbidden. 7. Unwilling to or unable to complete the entire trial procedure according to the protocol. 8. In investigator's opinion, the patient is not proper for the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PID From Pre-dose Baseline at 20 Minutes After First Injection. | Baseline and 20 minutes after the first injection | 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'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PID From Pre-dose Baseline at 30 Minutes After First Injection. | Baseline and 30 minutes after the first injection | 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'. |
| PID From Pre-dose Baseline at 60 Minutes After First Injection. | Baseline and 60 minutes after the first injection | 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'. |
| PID From Pre-dose Baseline at 10 Minutes After First Injection. | Baseline and 10 minutes after the first injection | 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'. |
| Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | 120 minutes after the first injection | 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). |
| Proportion of Patients Who Need the Second Injection | 20 minutes after the first injection. | Proportion of patients who need the second injection at 20 minutes after the first injection. |
| PID From Pre-dose Baseline at 120 Minutes After First Injection. | Baseline and 120 minutes after the first injection | 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'. |
Countries
China
Participant flow
Recruitment details
299 patients were entered and 295 were treated.
Participants by arm
| Arm | Count |
|---|---|
| Buscopan® (Hyoscine Butylbromide) 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 | 153 |
| 654-II (Anisodamine) 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 | 142 |
| Total | 295 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Not Treated | 1 | 3 |
| Overall Study | Protocol Violation | 9 | 14 |
Baseline characteristics
| Characteristic | Buscopan® (Hyoscine Butylbromide) | 654-II (Anisodamine) | Total |
|---|---|---|---|
| Age, Continuous | 41.5 Years STANDARD_DEVIATION 14.2 | 40.7 Years STANDARD_DEVIATION 14.8 | 41.1 Years STANDARD_DEVIATION 14.4 |
| Sex: Female, Male Female | 90 Participants | 76 Participants | 166 Participants |
| Sex: Female, Male Male | 63 Participants | 66 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 153 | 10 / 142 |
| serious Total, serious adverse events | 1 / 153 | 0 / 142 |
Outcome results
Primary
PID From Pre-dose Baseline at 20 Minutes After First Injection.
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | PID From Pre-dose Baseline at 20 Minutes After First Injection. | -4.09 Units on a scale | Standard Error 0.17 |
| 654-II (Anisodamine) | PID From Pre-dose Baseline at 20 Minutes After First Injection. | -3.66 Units on a scale | Standard Error 0.18 |
Comparison: Restricted maximum likelihood (REML) -repeated measures approachp-value: <0.000195% CI: [-0.88, 0.04]Mixed Models Analysis
p-value: 0.074395% CI: [-0.88, 0.04]Mixed Models Analysis
Secondary
Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Very Good | 22.5 Percentage of Patients |
| Buscopan® (Hyoscine Butylbromide) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Good | 59.2 Percentage of Patients |
| Buscopan® (Hyoscine Butylbromide) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Fair | 18.3 Percentage of Patients |
| Buscopan® (Hyoscine Butylbromide) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Poor | 0.0 Percentage of Patients |
| 654-II (Anisodamine) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Poor | 4.7 Percentage of Patients |
| 654-II (Anisodamine) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Very Good | 22.0 Percentage of Patients |
| 654-II (Anisodamine) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Fair | 29.1 Percentage of Patients |
| 654-II (Anisodamine) | Global Assessment of Efficacy by the Patient at 120 Minutes After the First Injection | Good | 44.1 Percentage of Patients |
p-value: 0.0113van Elteren test
Secondary
PID From Pre-dose Baseline at 10 Minutes After First Injection.
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | PID From Pre-dose Baseline at 10 Minutes After First Injection. | -2.64 Units on a scale | Standard Error 0.14 |
| 654-II (Anisodamine) | PID From Pre-dose Baseline at 10 Minutes After First Injection. | -2.33 Units on a scale | Standard Error 0.15 |
p-value: 0.12195% CI: [-0.7, 0.08]Mixed Models Analysis
Secondary
PID From Pre-dose Baseline at 120 Minutes After First Injection.
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | PID From Pre-dose Baseline at 120 Minutes After First Injection. | -6.46 Units on a scale | Standard Error 0.13 |
| 654-II (Anisodamine) | PID From Pre-dose Baseline at 120 Minutes After First Injection. | -6.01 Units on a scale | Standard Error 0.14 |
p-value: 0.014995% CI: [-0.81, -0.09]Mixed Models Analysis
Secondary
PID From Pre-dose Baseline at 30 Minutes After First Injection.
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | PID From Pre-dose Baseline at 30 Minutes After First Injection. | -5.14 Units on a scale | Standard Error 0.15 |
| 654-II (Anisodamine) | PID From Pre-dose Baseline at 30 Minutes After First Injection. | -4.74 Units on a scale | Standard Error 0.16 |
p-value: 0.065895% CI: [-0.82, 0.03]Mixed Models Analysis
Secondary
PID From Pre-dose Baseline at 60 Minutes After First Injection.
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | PID From Pre-dose Baseline at 60 Minutes After First Injection. | -5.96 Units on a scale | Standard Error 0.14 |
| 654-II (Anisodamine) | PID From Pre-dose Baseline at 60 Minutes After First Injection. | -5.51 Units on a scale | Standard Error 0.15 |
p-value: 0.02295% CI: [-0.85, -0.07]Mixed Models Analysis
Secondary
Proportion of Patients Who Need the Second Injection
Proportion of patients who need the second injection at 20 minutes after the first injection.
Time frame: 20 minutes after the first injection.
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Buscopan® (Hyoscine Butylbromide) | Proportion of Patients Who Need the Second Injection | 24.6 Percentage of Patients |
| 654-II (Anisodamine) | Proportion of Patients Who Need the Second Injection | 33.9 Percentage of Patients |
p-value: 0.099295% CI: [0.37, 1.09]Regression, Logistic