Healthy
Conditions
Brief summary
Determine bioequivalence of two forumulations with hyoscine butylbromide 10mg sugar coated tablets.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
healthy males and females, aged 18-50years, BMI 18,5-30
Exclusion criteria
History of hypersensitivity or allergy to IMP
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration of Hyoscine Butylbromide (Cmax) | Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter | The maximum measured concentration of hyoscine butylbromide in plasma. |
| AUC Time Zero to Times of Last Quantifiable Concentration (AUC 0-t) | Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter | Area under the concentration-time curve of hyoscine butylbromide in plasma over the time interval from 0 to the last quantifiable data point (AUC0-t). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC0-∞). | Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter | The area under the concentration-time curve of hyoscine butylbromide in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
| Area Under the Curve, for the Test Product, to the Time of the Maximum Concentration of the Reference Product and the Test Product (AUCReftmax) | Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter | Area under the concentration-time curve of hyoscine butylbromide to the time of the maximum concentration of hyoscine butylbromide of the reference product (Buscopan®). This was calculated both for test and reference products. |
Countries
Canada
Participant flow
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects who meet the inclusion criteria will be considered eligible to participate in the study. Subjects who meet one or more of the exclusion criteria will not be considered eligible to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| REF-T The subjects received the reference treatment (REF) which was 20 milligram (mg) of hyoscine butylbromide (trade name: Buscopan®, 2\*10mg) followed by a washout period of 7 to 14 days followed by the test treatment (T) which was 20 mg of hyoscine butylbromide (trade name: Buscapina®, 2\*10mg) followed by a washout period of 7 to 14 days.
All medications were administered as a single oral dose in the fasted state via a sugar coated tablet. | 28 |
| T-REF The subjects received test treatment (T) which was 20 milligram (mg) of hyoscine butylbromide (trade name: Buscapina®, 2\*10mg) followed by a washout period of 7 to 14 days followed by the reference treatment (REF) which was 20 mg of hyoscine butylbromide (trade name: Buscopan®, 2\*10mg) followed by a washout period of 7 to 14 days.
All medications were administered as a single oral dose in the fasted state via a sugar coated tablet. | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Protocol Violation | 1 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 1 |
| Washout After Period 1 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | REF-T | T-REF | Total |
|---|---|---|---|
| Age, Continuous | 26.7 years STANDARD_DEVIATION 7.17 | 24.5 years STANDARD_DEVIATION 3.9 | 25.6 years STANDARD_DEVIATION 5.83 |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 22 Participants | 20 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 56 | 0 / 56 |
| serious Total, serious adverse events | 0 / 56 | 0 / 56 |
Outcome results
Primary
AUC Time Zero to Times of Last Quantifiable Concentration (AUC 0-t)
Area under the concentration-time curve of hyoscine butylbromide in plasma over the time interval from 0 to the last quantifiable data point (AUC0-t).
Time frame: Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter
Population: PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (REF) | AUC Time Zero to Times of Last Quantifiable Concentration (AUC 0-t) | 807 hour (h)*pg/mL | Geometric Coefficient of Variation 89.3 |
| Buscapina® (T) | AUC Time Zero to Times of Last Quantifiable Concentration (AUC 0-t) | 725 hour (h)*pg/mL | Geometric Coefficient of Variation 89.1 |
Comparison: The study design is a two-stage Pocock-like group sequential design according to the alpha spending function approach. The alpha level for Stage 1 was 0.0377 (one-sided).92.46% CI: [83.51, 100.78]
Primary
Maximum Observed Plasma Concentration of Hyoscine Butylbromide (Cmax)
The maximum measured concentration of hyoscine butylbromide in plasma.
Time frame: Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter
Population: All subjects who had evaluable pharmacokinetic (PK) data for at least one of the treatment periods were included in the PK population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (REF) | Maximum Observed Plasma Concentration of Hyoscine Butylbromide (Cmax) | 91 picogram (pg)/millilitre (mL) | Geometric Coefficient of Variation 93.4 |
| Buscapina® (T) | Maximum Observed Plasma Concentration of Hyoscine Butylbromide (Cmax) | 80 picogram (pg)/millilitre (mL) | Geometric Coefficient of Variation 100.6 |
Comparison: The study design is a two-stage Pocock-like group sequential design according to the alpha spending function approach. The alpha level for Stage 1 was 0.0377 (one-sided).92.46% CI: [77.18, 99.24]
Secondary
Area Under the Curve, for the Test Product, to the Time of the Maximum Concentration of the Reference Product and the Test Product (AUCReftmax)
Area under the concentration-time curve of hyoscine butylbromide to the time of the maximum concentration of hyoscine butylbromide of the reference product (Buscopan®). This was calculated both for test and reference products.
Time frame: Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter
Population: PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (REF) | Area Under the Curve, for the Test Product, to the Time of the Maximum Concentration of the Reference Product and the Test Product (AUCReftmax) | 187 h*pg/mL | Geometric Coefficient of Variation 104 |
| Buscapina® (T) | Area Under the Curve, for the Test Product, to the Time of the Maximum Concentration of the Reference Product and the Test Product (AUCReftmax) | 170 h*pg/mL | Geometric Coefficient of Variation 121.8 |
Comparison: The test product was compared to the reference product by means of statistical analysis.92.46% CI: [81.94, 105.47]
Secondary
Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC0-∞).
The area under the concentration-time curve of hyoscine butylbromide in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Blood sampling within 2 hours prior to dosing, and 30, 60, and 120 minutes, and at 2.5, 3, 3.5, 3.75, 4, 4.25, 4.5, 5, 5.5, 6, 8, 12, 24, 36, 48 and 60 hours thereafter
Population: PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Buscopan® (REF) | Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC0-∞). | 847 h*pg/mL | Geometric Coefficient of Variation 86.6 |
| Buscapina® (T) | Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC0-∞). | 760 h*pg/mL | Geometric Coefficient of Variation 88.5 |
Comparison: The test product was compared to the reference product by means of statistical analysis.92.46% CI: [83.59, 100.51]