Relative Bioavailability Study to Investigate and to Compare Two Different Formulations of Hyoscine Butylbromide in Healthy Male and Female Volunteers
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01734902
Collaborator
(none)
30
1
2
30
30.4
Study Details
Study Description
Brief Summary
The objective of the current trial is to establish the bioequivalence of 2 hyoscine butylbromide dose forms following oral administration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Relative Bioavailability Study to Investigate and to Compare Two Different Formulations of Hyoscine Butylbromide, Following Oral Administration in Healthy Male and Female Volunteers (an Open-label, Randomised, Single Dose, Two-way Crossover, Phase I Study)
Actual Study Start Date
:
Nov 1, 2012
Actual Primary Completion Date
:
Dec 1, 2012
Actual Study Completion Date
:
Dec 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Hyoscine butylbromide drops, oral administration with 240 mL water |
Drug: Hyoscine butylbromide
drops for oral administration
|
| Experimental: 2 Hyoscine butylbromide sugar coated tablets, oral administration with 240 mL water |
Drug: Hyoscine butylbromide
sugar coated tablets for oral administration
|
Outcome Measures
Primary Outcome Measures
- Maximum Measured Concentration of the Hyoscine Butylbromide in Plasma (Cmax) [Pharmacokinetic samples were collected pre dose at 2 hour (h) and at 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 14, 24 and 36 h after the drug administration.]
Cmax, maximum measured concentration of the hyoscine butylbromide in plasma.
- Area Under the Concentration-time Curve of the Hyoscine Butylbromide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) [Pharmacokinetic samples were collected pre dose at 2 hour (h) and at 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 14, 24 and 36 h after the drug administration.]
AUC0-tz, area under the concentration-time curve of the hyoscine butylbromide in plasma over the time interval from 0 to the last quantifiable data point
Secondary Outcome Measures
- Area Under the Concentration-time Curve of the Hyoscine Butylbromide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ ) [Pharmacokinetic samples were collected pre dose at 2 hour (h) and at 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 14, 24 and 36 h after the drug administration.]
AUC0-∞, area under the concentration-time curve of the hyoscine butylbromide in plasma over the time interval from 0 extrapolated to infinity
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
- Healthy male and female subjects
Exclusion criteria:
- Any relevant deviation from healthy conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 202.846.1 Boehringer Ingelheim Investigational Site | Ingelheim | Germany |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01734902
Other Study ID Numbers:
- 202.846
- 2012-003720-20
First Posted:
Nov 28, 2012
Last Update Posted:
Apr 23, 2019
Last Verified:
Apr 1, 2019
Study Results
Participant Flow
| Recruitment Details | Randomised, single-dose, open-label, two-way crossover trial in healthy volunteers to investigate and compare the relative bioavailability of two formulations of hyoscine butylbromide administered orally as drops (T: test treatment) or as sugar-coated Buscopan® tablets(R: reference treatment). |
|---|---|
| Pre-assignment Detail | All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomized to trial treatment if any one of the specific entry criteria were not met. |
| Arm/Group Title | Buscopan® Tablet (R)/Hyoscine Butylbromide Drops (T) | Hyoscine Butylbromide Drops (T)/Buscopan® Tablet (R) |
|---|---|---|
| Arm/Group Description | Participants administered orally in the morning on Day 1 of period 1 with single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan®, followed by 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) in the morning on Day 1 of period 2, each treatment with 240 mL water. Both treatment periods were separated by a wash-out period of at least 7 days. | Participants administered orally in the morning on Day 1 of period 1 with 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) orally, followed by single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan® in the morning on Day 1 of period 2, each treatment with 240 mL water. Both treatment periods were separated by a wash-out period of at least 7 days. |
| Period Title: Overall Study | ||
| STARTED | 14 | 16 |
| COMPLETED | 14 | 14 |
| NOT COMPLETED | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | Buscopan® Tablet (R)/Hyoscine Butylbromide Drops (T) | Hyoscine Butylbromide Drops (T)/Buscopan® Tablet (R) | Total |
|---|---|---|---|
| Arm/Group Description | Participants administered orally in the morning on Day 1 of period 1 with single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan®, followed by 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) in the morning on Day 1 of period 2, each treatment with 240 mL water. Both treatment periods were separated by a wash-out period of at least 7 days. | Participants administered orally in the morning on Day 1 of period 1 with 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) orally, followed by single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan® in the morning on Day 1 of period 2, each treatment with 240 mL water. Both treatment periods were separated by a wash-out period of at least 7 days. | Total of all reporting groups |
| Overall Participants | 14 | 16 | 30 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
38.1
(8.0)
|
37.8
(7.5)
|
37.9
(7.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
9
64.3%
|
7
43.8%
|
16
53.3%
|
| Male |
5
35.7%
|
9
56.3%
|
14
46.7%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
14
100%
|
16
100%
|
30
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Maximum Measured Concentration of the Hyoscine Butylbromide in Plasma (Cmax) |
|---|---|
| Description | Cmax, maximum measured concentration of the hyoscine butylbromide in plasma. |
| Time Frame | Pharmacokinetic samples were collected pre dose at 2 hour (h) and at 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 14, 24 and 36 h after the drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Descriptive statistics is based on treated set (TS) and statistical analysis is based on pharmacokinetic (PK) analysis set (PKS). (PKS includes all treated subjects with data for a primary endpoint and without any protocol violation relevant to the statistical evaluation of PK endpoints.) |
| Arm/Group Title | Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) |
|---|---|---|
| Arm/Group Description | Participants administered orally single dose of 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) with 240 mL water in the morning on Day 1 of period 1 or period 2. | Participants administered orally single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan® with 240 mL water in the morning on Day 1 of period 1 or period 2. |
| Measure Participants | 28 | 28 |
| Geometric Mean (Geometric Coefficient of Variation) [Picogram/millilitre [pg/mL]] |
70.3
(140.0)
|
77.1
(167.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Hyoscine Butylbromide Drops (T), Buscopan® Tablet (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The statistical model, analysis of variance (ANOVA) on the logarithmic scale includes effects: 'sequence', 'subjects within sequences', 'period', and 'treatment'. The effect 'subject within sequences' was considered as random, whereas the other effects were considered as fixed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted gMean ratio T/R (%) |
| Estimated Value | 86.97 | |
| Confidence Interval |
(2-Sided) 90% 74.046 to 102.151 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 35.6 |
|
| Estimation Comments | Standard error of the mean is actually intra-individual geometric coefficient variance [%]. Statistical analysis is based on PKS which includes 27 subjects. | |
| Title | Area Under the Concentration-time Curve of the Hyoscine Butylbromide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) |
|---|---|
| Description | AUC0-tz, area under the concentration-time curve of the hyoscine butylbromide in plasma over the time interval from 0 to the last quantifiable data point |
| Time Frame | Pharmacokinetic samples were collected pre dose at 2 hour (h) and at 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 14, 24 and 36 h after the drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Descriptive statistics is based on TS and statistical analysis is based on pharmacokinetic (PK) analysis set (PKS). (PKS includes all treated subjects with data for a primary endpoint and without any protocol violation relevant to the statistical evaluation of PK endpoints.) |
| Arm/Group Title | Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) |
|---|---|---|
| Arm/Group Description | Participants administered orally single dose of 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) with 240 mL water in the morning on Day 1 of period 1 or period 2. | Participants administered orally single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan® with 240 mL water in the morning on Day 1 of period 1 or period 2. |
| Measure Participants | 28 | 28 |
| Geometric Mean (Geometric Coefficient of Variation) [Picogram*hour/millilitre [pg*h/mL]] |
564.0
(131.0)
|
608.0
(139.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Hyoscine Butylbromide Drops (T), Buscopan® Tablet (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The statistical model, analysis of variance (ANOVA) on the logarithmic scale includes effects: 'sequence', 'subjects within sequences', 'period', and 'treatment'. The effect 'subject within sequences' was considered as random, whereas the other effects were considered as fixed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted gMean ratio T/R (%) |
| Estimated Value | 89.05 | |
| Confidence Interval |
(2-Sided) 90% 77.26 to 102.62 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 31.2 |
|
| Estimation Comments | Standard error of the mean is actually intra-individual geometric coefficient variance [%]. Statistical analysis is based on PKS which includes 27 subjects. | |
| Title | Area Under the Concentration-time Curve of the Hyoscine Butylbromide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ ) |
|---|---|
| Description | AUC0-∞, area under the concentration-time curve of the hyoscine butylbromide in plasma over the time interval from 0 extrapolated to infinity |
| Time Frame | Pharmacokinetic samples were collected pre dose at 2 hour (h) and at 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 14, 24 and 36 h after the drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Descriptive statistics is based on TS and statistical analysis is based on pharmacokinetic (PK) analysis set (PKS). (PKS includes all treated subjects with data for a primary endpoint and without any protocol violation relevant to the statistical evaluation of PK endpoints.) |
| Arm/Group Title | Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) |
|---|---|---|
| Arm/Group Description | Participants administered orally single dose of 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) with 240 mL water in the morning on Day 1 of period 1 or period 2. | Participants administered orally single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan® with 240 mL water in the morning on Day 1 of period 1 or period 2. |
| Measure Participants | 28 | 28 |
| Geometric Mean (Geometric Coefficient of Variation) [Picogram*hour/millilitre [pg*h/mL]] |
623.0
(122.0)
|
668.0
(125.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Hyoscine Butylbromide Drops (T), Buscopan® Tablet (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | The statistical model, analysis of variance (ANOVA) on the logarithmic scale includes effects: 'sequence', 'subjects within sequences', 'period', and 'treatment'. The effect 'subject within sequences' was considered as random, whereas the other effects were considered as fixed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted gMean ratio T/R [%] |
| Estimated Value | 90.03 | |
| Confidence Interval |
(2-Sided) 90% 78.78 to 102.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 29.3 |
|
| Estimation Comments | Standard error of the mean is actually intra-individual geometric coefficient variance [%]. Statistical analysis is based on PKS which includes 27 subjects. | |
Adverse Events
| Time Frame | From the first dose of trial medication until 7 days after the end of treatment period, upto 9 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) | ||
| Arm/Group Description | Participants administered orally single dose of 20 mg hyoscine butylbromide drops with dose strength of 2 millilitre (mL) with 240 mL water in the morning on Day 1 of period 1 or period 2. | Participants administered orally single dose of 2 sugar-coated tablets of 10 milligram (20 mg) of Buscopan® with 240 mL water in the morning on Day 1 of period 1 or period 2. | ||
All Cause Mortality |
||||
| Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | 0/28 (0%) | ||
Serious Adverse Events |
||||
| Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | 0/28 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Hyoscine Butylbromide Drops (T) | Buscopan® Tablet (R) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/30 (10%) | 3/28 (10.7%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 1/30 (3.3%) | 2/28 (7.1%) | ||
| Nervous system disorders | ||||
| Headache | 3/30 (10%) | 1/28 (3.6%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
| Name/Title | Boehringer Ingelheim, Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01734902
Other Study ID Numbers:
- 202.846
- 2012-003720-20
First Posted:
Nov 28, 2012
Last Update Posted:
Apr 23, 2019
Last Verified:
Apr 1, 2019