Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bioequivalence of a Fixed Dose Combination Tablet Containing 400 mg Ibuprofen and 60 mg Pseudoephedrine-HCl Compared to Two Film Coated Fixed Dose Combination Tablets RhinAdvil(R)(200 mg Ibuprofen and 30 mg Pseudoephedrine-HCl) Administered in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02963701
Recruitment Status : Completed
First Posted : November 15, 2016
Results First Posted : September 27, 2018
Last Update Posted : September 27, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Primary Purpose: Treatment
Condition Healthy Volunteers
Interventions Drug: Ibuprofen
Drug: Pseudoephedrine-HCl
Enrollment 56
Recruitment Details  
Pre-assignment Details This study was an Open-label, randomised, laboratory blind, single dose, two-way crossover, Phase I trial. A total of 56 healthy male and female subjects were randomised in the trial. Subjects were assigned randomly to one of two treatment sequences (Test-Reference, Reference-Test), before first drug administration.
Arm/Group Title Treatment Sequence 1 (T-R) Treatment Sequence 2 (R-T)
Hide Arm/Group Description Treatment sequence (Test-Reference): The subjects were administered orally under fasting condition first with Test product: Ibuprofen 400 milligram and Pseudoephedrine-HCl 60 milligram fixed dose combination film coated tablet and then with Reference product: 2 x RhinAdvil® (Ibuprofen 200 milligram and Pseudoephedrine-HCl 30 milligram fixed dose combination film coated tablets). Treatments were separated by a washout period of at least 5 days. Treatment sequence (Reference-Test): The subjects were administered orally under fasting condition first with Reference product : 2 x RhinAdvil® (Ibuprofen 200 milligram and Pseudoephedrine-HCl 30 milligram fixed dose combination film coated tablets) and then with Test product: Ibuprofen 400 milligram and Pseudoephedrine-HCl 60 milligram fixed dose combination film coated tablet. Treatments were separated by a washout period of at least 5 days.
Period Title: Period 1 (Including Washout) (2 Days)
Started 28 28
Completed 27 [1] 28
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
[1]
One subject withdrawn from the study after period 1
Period Title: Period 2 (2 Days)
Started 27 28
Completed 27 28
Not Completed 0 0
Arm/Group Title Treatment Sequence 1 (T-R) Treatment Sequence 2 (R-T) Total
Hide Arm/Group Description Treatment sequence (Test-Reference): The subjects were administered orally under fasting condition first with Test product: Ibuprofen 400 milligram and Pseudoephedrine-HCl 60 milligram fixed dose combination film coated tablet and then with Reference product: 2 x RhinAdvil® (Ibuprofen 200 milligram and Pseudoephedrine-HCl 30 milligram fixed dose combination film coated tablets). Treatments were separated by a washout period of at least 5 days. Treatment sequence (Reference-Test): The subjects were administered orally under fasting condition first with Reference product : 2 x RhinAdvil® (Ibuprofen 200 milligram and Pseudoephedrine-HCl 30 milligram fixed dose combination film coated tablets) and then with Test product: Ibuprofen 400 milligram and Pseudoephedrine-HCl 60 milligram fixed dose combination film coated tablet. Treatments were separated by a washout period of at least 5 days. Total of all reporting groups
Overall Number of Baseline Participants 28 28 56
Hide Baseline Analysis Population Description
Baseline characteristics were calculated on Safety Population. All subjects who received at least one dose of study medication were included in the safety population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants 28 participants 56 participants
28.5  (6.77) 29.2  (8.03) 28.8  (7.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 28 participants 56 participants
Female
12
  42.9%
12
  42.9%
24
  42.9%
Male
16
  57.1%
16
  57.1%
32
  57.1%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants 28 participants 56 participants
American Indian or Alaska Native 0 0 0
Asian 0 0 0
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 20 21 41
White 7 6 13
More than one race 0 0 0
Other 1 1 2
[1]
Measure Description: Ethnicity data was not collected as per protocol.
1.Primary Outcome
Title Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Ibuprofen. (AUC0-tz)
Hide Description This endpoint calculates area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 to the time of last quantifiable time point.
Time Frame Samples were collected Pre-dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour nano gram per milliliter (h*ng/mL)
140500
(23.66%)
139300
(19.30%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 99.16
Confidence Interval (2-Sided) 90%
96.52 to 101.89
Parameter Dispersion
Type: Standard Deviation
Value: 8.49
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
2.Primary Outcome
Title Maximum Concentration of Ibuprofen in Plasma (Cmax).
Hide Description This outcome is maximum measured concentration of the Ibuprofen in plasma
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nano gram per milliliter (ng/mL)
33580
(26.16%)
29940
(20.80%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 89.16
Confidence Interval (2-Sided) 90%
83.88 to 94.76
Parameter Dispersion
Type: Standard Deviation
Value: 19.28
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
3.Primary Outcome
Title Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Pseudoephedrine (AUC0-tz).
Hide Description This endpoint calculates area under the concentration-time curve of Pseudoephedrine in plasma over the time interval from 0 to the time of last quantifiable time point.
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
2547
(22.22%)
2540
(22.45%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 99.75
Confidence Interval (2-Sided) 90%
95.73 to 103.95
Parameter Dispersion
Type: Standard Deviation
Value: 12.96
Estimation Comments The estimated parameter was the adjusted geometric mean ratios [%] of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation [%].
4.Primary Outcome
Title Maximum Concentration of Pseudoephedrine in Plasma (Cmax).
Hide Description This outcome is maximum measured concentration of the Pseudoephedrine in plasma
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
320.4
(22.09%)
327.4
(25.28%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 102.16
Confidence Interval (2-Sided) 90%
97.30 to 107.27
Parameter Dispersion
Type: Standard Deviation
Value: 15.37
Estimation Comments The estimated parameter was the adjusted geometric mean ratios [%] of Test and Reference products. The parameter dispersion type [SD] was actually the intra-individual geometric coefficient of variation [%].
5.Secondary Outcome
Title Area Under the Concentration-time Curve of Ibuprofen in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
Hide Description This endpoint calculates area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 extrapolated to infinity
Time Frame Samples were collected Pre-dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
143000
(22.88%)
141600
(18.72%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 98.97
Confidence Interval (2-Sided) 90%
96.44 to 101.57
Parameter Dispersion
Type: Standard Deviation
Value: 8.13
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%)of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
6.Secondary Outcome
Title Area Under the Concentration-time Curve of Pseudoephedrine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
Hide Description This endpoint calculates area under the concentration-time curve of Pseudoephedrine in plasma over the time interval from 0 extrapolated to infinity
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
2622
(23.07%)
2614
(23.65%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 99.67
Confidence Interval (2-Sided) 90%
95.48 to 104.04
Parameter Dispersion
Type: Standard Deviation
Value: 13.50
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
7.Secondary Outcome
Title AUC0-tz of R-Ibuprofen
Hide Description This endpoint calculates area under the concentration-time curve of R-Ibuprofen in plasma over the time interval from 0 to the time of last quantifiable time point.
Time Frame Samples were collected Pre-dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
68520
(28.08%)
65760
(21.55%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 95.96
Confidence Interval (2-Sided) 90%
91.70 to 100.40
Parameter Dispersion
Type: Standard Deviation
Value: 14.27
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
8.Secondary Outcome
Title AUC0-∞ of R-Ibuprofen
Hide Description This endpoint calculates area under the concentration-time curve of R-Ibuprofen in plasma over the time interval from 0 extrapolated to infinity
Time Frame Samples were collected Pre-dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
69420
(27.76%)
66740
(21.51%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 96.12
Confidence Interval (2-Sided) 90%
91.92 to 100.51
Parameter Dispersion
Type: Standard Deviation
Value: 14.06
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
9.Secondary Outcome
Title Cmax of R-Ibuprofen
Hide Description This outcome is maximum measured concentration of the R-Ibuprofen in plasma
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
18630
(29.34%)
16910
(21.98%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 90.83
Confidence Interval (2-Sided) 90%
84.87 to 97.21
Parameter Dispersion
Type: Standard Deviation
Value: 21.49
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
10.Secondary Outcome
Title AUC0-tz of S-Ibuprofen
Hide Description This endpoint calculates area under the concentration-time curve of S-Ibuprofen in plasma over the time interval from 0 to the time of last quantifiable time point.
Time Frame Samples were collected Pre-dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
70290
(24.90%)
71610
(23.25%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 101.86
Confidence Interval (2-Sided) 90%
99.33 to 104.46
Parameter Dispersion
Type: Standard Deviation
Value: 7.89
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
11.Secondary Outcome
Title AUC0-∞ of S-Ibuprofen
Hide Description This endpoint calculates area under the concentration-time curve of S-Ibuprofen in plasma over the time interval from 0 extrapolated to infinity
Time Frame Samples were collected Pre-dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
72270
(23.84%)
73460
(22.21%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 101.65
Confidence Interval (2-Sided) 90%
99.40 to 103.95
Parameter Dispersion
Type: Standard Deviation
Value: 7.01
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
12.Secondary Outcome
Title Cmax of S-Ibuprofen
Hide Description This outcome is maximum measured concentration of the S-Ibuprofen in plasma
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
15050
(22.28%)
13020
(22.36%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter T/R Ratio (%)
Estimated Value 86.53
Confidence Interval (2-Sided) 90%
82.03 to 91.28
Parameter Dispersion
Type: Standard Deviation
Value: 16.85
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
13.Secondary Outcome
Title S/R-ibuprofen Ratio for AUC0-tz
Hide Description AUC0-tz S-ibuprofen / AUC0-tz R-ibuprofen
Time Frame Samples were collected pre dose and at 0:10, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 30:00 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population (PK Set): All treated subjects that provided observations for both periods for at least one primary endpoint evaluable and without any major protocol deviation thought to interfere with the absorption, distribution, metabolism, and excretion of the compound to be measured were included in the PK population.
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description:
Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets)
Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
Overall Number of Participants Analyzed 55 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
1.026
(23.26%)
1.089
(23.30%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product (R), Test Product (T)
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A claim of bioequivalence was made if the 90% confidence interval (CI) of the geometric means of T/R ratio was contained in the pre-defined acceptance range of 80.00% to 125.00%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Results are based on ANOVA model on the logarithmic scale including fixed effects for sequence, subject nested within sequence, period and treatment.
Method of Estimation Estimation Parameter Ratio (%)
Estimated Value 106.17
Confidence Interval (2-Sided) 90%
101.30 to 111.26
Parameter Dispersion
Type: Standard Deviation
Value: 14.77
Estimation Comments The estimated parameter was the adjusted geometric mean ratios (%) of Test and Reference products. The parameter dispersion type (Standard Deviation) was actually the intra-individual geometric coefficient of variation (%).
Time Frame From first drug administration till 7 days after last drug administration; up to 14 days
Adverse Event Reporting Description

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.

All subjects who received at least one dose of study medication were included in the safety population.

 
Arm/Group Title Reference Product (R) Test Product (T)
Hide Arm/Group Description Subjects were orally administered with RhinAdvil® (Ibuprofen 200 mg and Pseudoephedrine-HCl 30 mg fixed dose combination film coated tablet) (2 tablets) Subjects were orally administered with Ibuprofen 400 mg and Pseudoephedrine-HCl 60 mg fixed dose combination film coated tablet (1 tablet)
All-Cause Mortality
Reference Product (R) Test Product (T)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/55 (0.00%)   0/56 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Reference Product (R) Test Product (T)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/55 (0.00%)   0/56 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Reference Product (R) Test Product (T)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/55 (0.00%)   0/56 (0.00%) 
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.
Other - 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
Name/Title: Boehringer Ingelheim Call Centre
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02963701     History of Changes
Other Study ID Numbers: 1024.9
First Submitted: November 10, 2016
First Posted: November 15, 2016
Results First Submitted: January 23, 2018
Results First Posted: September 27, 2018
Last Update Posted: September 27, 2018