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Trial record 69 of 3089 for:    Area Under Curve AND Healthy

DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)

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: NCT02574845
Recruitment Status : Completed
First Posted : October 14, 2015
Results First Posted : February 13, 2017
Last Update Posted : February 13, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Rosuvastatin
Drug: Metformin HCl
Drug: Furosemide
Enrollment 18
Recruitment Details All subjects were screened for eligibility to participate in the study. No run-in or wash-out period was conducted, since the trial was conducted in healthy subjects, that were not expected to take medications regularly. Actual number of subjects enrolled in fact represents randomized subjects due to the study set up.
Pre-assignment Details All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subjects) met all strictly implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were violated.
Arm/Group Title Treatment (T) 1-T3-Reference (REF)-T5-T2-T4 T2-REF-T4-T1-T5-T3 T3-T5-T1-T4-REF-T2 T4-T2-T5-REF-T3-T1 T5-T4-T3-T2-T1-REF REF-T1-T2-T3-T4-T5
Hide Arm/Group Description The subjects received test treatment 1 (T1) which is 10 milligram (mg) metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor) followed by test treatment 3 (T3) which is 500mg metformin hydrochloride together with REF followed by REF alone followed by test treatment 5 (T5) which is 5 mg furosemide (oral solution, brand name: Lasix liquidum) together with REF followed by test treatment 2 (T2) which is 50 mg of metformin hydrochloride together with REF followed by test treatment 4 (T4) which is 1mg of furosemide together with REF. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T2, followed by REF alone, followed by T4, followed by T1, followed by T5 and followed by T3. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T3, followed by T5, followed by T1, followed by T4, followed by REF alone and followed by T2. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T4, followed by T2, followed by T5, followed by REF alone, followed by T3 and followed by T1. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T5, followed by T4, followed by T3, followed by T2, followed by T1 and followed by REF alone. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received REF alone, followed by T1, followed by T2, followed by T3, followed by T4 and followed by T5. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations.
Period Title: Overall Study
Started 3 3 3 3 3 3
Received T1 3 2 3 3 2 2 [1]
Received T2 3 3 3 3 2 3
Received T3 2 [1] 2 3 3 2 3
Received T4 3 2 3 3 2 2
Received T5 3 2 3 3 3 2
Received R 3 2 3 3 2 3
Completed 3 2 3 3 2 2
Not Completed 0 1 0 0 1 1
Reason Not Completed
Consent withdrawn further participation             0             0             0             0             1             0
Adverse Event             0             1             0             0             0             1
[1]
one subject missed treatment period 2
Arm/Group Title Treatment (T) 1-T3-Reference (REF)-T5-T2-T4 T2-REF-T4-T1-T5-T3 T3-T5-T1-T4-REF-T2 T4-T2-T5-REF-T3-T1 T5-T4-T3-T2-T1-REF REF-T1-T2-T3-T4-T5 Total
Hide Arm/Group Description The subjects received test treatment 1 (T1) which is 10 milligram (mg) metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor) followed by test treatment 3 (T3) which is 500mg metformin hydrochloride together with REF followed by REF alone followed by test treatment 5 (T5) which is 5 mg furosemide (oral solution, brand name: Lasix liquidum) together with REF followed by test treatment 2 (T2) which is 50 mg of metformin hydrochloride together with REF followed by test treatment 4 (T4) which is 1mg of furosemide together with REF. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T2, followed by REF alone, followed by T4, followed by T1, followed by T5 and followed by T3. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T3, followed by T5, followed by T1, followed by T4, followed by REF alone and followed by T2. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T4, followed by T2, followed by T5, followed by REF alone, followed by T3 and followed by T1. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received T5, followed by T4, followed by T3, followed by T2, followed by T1 and followed by REF alone. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. The subjects received REF alone, followed by T1, followed by T2, followed by T3, followed by T4 and followed by T5. Trial medication was administered as a single oral dose in the fasted state in each treatment period. The six single dose treatment periods were separated from each other by a wash-out period of at least 6 days between the drug administrations. Total of all reporting groups
Overall Number of Baseline Participants 3 3 3 3 3 3 18
Hide Baseline Analysis Population Description
The randomised set (RS) includes all randomised subjects, whether treated or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 18 participants
28.0  (2.6) 33.0  (8.7) 39.3  (10.3) 32.0  (14.1) 22.0  (2.6) 37.3  (12.9) 31.9  (10.0)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 18 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
18
 100.0%
1.Primary Outcome
Title Area Under the Curve of Rosuvastatin From 0 to the Last Quantifiable Data Point (AUC0-tz)
Hide Description This outcome measure presents the area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time Frame Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) parameter set (PKS) includes all randomised subjects who took at least one dose of study medication and provided at least one primary or secondary PK parameter that was not excluded from analysis due to non-evaluability or protocol violation relevant for the evaluation of the pharmacokinetics.
Arm/Group Title REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Hide Arm/Group Description:
The subjects received the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 1 which is 10 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 2 which is 50 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 3 which is 500 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 4 which is 1 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 5 which is 5 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
Overall Number of Participants Analyzed 16 15 16 15 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomol (nmol) * hour (h) / Litre (L)
81.5
(50.9%)
87.8
(54.5%)
88.7
(62.4%)
126
(66.7%)
91.5
(55.4%)
97.2
(52.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 1
Comments This statistical analysis assess the effect of coadministration of 10 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Analysis of variance (ANOVA) model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T1/REF (%)
Estimated Value 101.95
Confidence Interval (2-Sided) 90%
89.49 to 116.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 2
Comments This statistical analysis assess the effect of coadministration of 50 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T2/REF (%)
Estimated Value 106.09
Confidence Interval (2-Sided) 90%
96.12 to 117.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 3
Comments This statistical analysis assess the effect of coadministration of 500 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T3/REF (%)
Estimated Value 152.18
Confidence Interval (2-Sided) 90%
135.12 to 171.41
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 4
Comments This statistical analysis assess the effect of coadministration of 1 mg furosemide on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T4/REF (%)
Estimated Value 106.97
Confidence Interval (2-Sided) 90%
94.34 to 121.30
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 5
Comments This statistical analysis assess the effect of coadministration of 5 mg furosemide on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T5/REF (%)
Estimated Value 115.92
Confidence Interval (2-Sided) 90%
101.93 to 131.82
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Concentration of Rosuvastatin (Cmax)
Hide Description This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax).
Time Frame Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Hide Arm/Group Description:
The subjects received the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 1 which is 10 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 2 which is 50 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 3 which is 500 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 4 which is 1 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 5 which is 5 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
Overall Number of Participants Analyzed 16 15 16 15 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
9.04
(52.4%)
9.59
(60.5%)
9.94
(69.4%)
14.0
(71.2%)
9.90
(62.0%)
10.8
(62.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 1
Comments This statistical analysis assess the effect of coadministration of 10 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T1/REF (%)
Estimated Value 102.47
Confidence Interval (2-Sided) 90%
87.19 to 120.42
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 2
Comments This statistical analysis assess the effect of coadministration of 50 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T2/REF (%)
Estimated Value 106.98
Confidence Interval (2-Sided) 90%
92.54 to 123.69
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 3
Comments This statistical analysis assess the effect of coadministration of 500 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T3/REF (%)
Estimated Value 154.07
Confidence Interval (2-Sided) 90%
131.70 to 180.24
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 4
Comments This statistical analysis assess the effect of coadministration of 1 mg furosemide on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T4/REF (%)
Estimated Value 106.81
Confidence Interval (2-Sided) 90%
91.78 to 124.30
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 5
Comments This statistical analysis assess the effect of coadministration of 5 mg furosemide on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T5/REF (%)
Estimated Value 117.98
Confidence Interval (2-Sided) 90%
98.27 to 141.65
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC0-∞)
Hide Description This outcome measure presents area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time Frame Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Hide Arm/Group Description:
The subjects received the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 1 which is 10 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 2 which is 50 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 3 which is 500 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 4 which is 1 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
The subjects received test treatment 5 which is 5 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
Overall Number of Participants Analyzed 15 14 16 14 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
99.7
(39.0%)
105
(48.0%)
102
(55.0%)
149
(49.8%)
108
(47.9%)
115
(42.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 1
Comments This statistical analysis assess the effect of coadministration of 10 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T1/REF (%)
Estimated Value 101.22
Confidence Interval (2-Sided) 90%
89.23 to 114.82
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 2
Comments This statistical analysis assess the effect of coadministration of 50 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T2/REF (%)
Estimated Value 107.26
Confidence Interval (2-Sided) 90%
97.65 to 117.81
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 3
Comments This statistical analysis assess the effect of coadministration of 500 mg metformin hydrochloride on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T3/REF (%)
Estimated Value 146.45
Confidence Interval (2-Sided) 90%
135.21 to 158.62
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 4
Comments This statistical analysis assess the effect of coadministration of 1 mg furosemide on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T4/REF (%)
Estimated Value 105.63
Confidence Interval (2-Sided) 90%
92.20 to 121.00
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection REF Alone, Treatment 5
Comments This statistical analysis assess the effect of coadministration of 5 mg furosemide on the primary outcome measure of the REF treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model on the logarithmic scale including the effects: 'sequence', 'subjects within sequence', 'period' and 'treatment'.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio T5/REF (%)
Estimated Value 118.10
Confidence Interval (2-Sided) 90%
106.75 to 130.67
Estimation Comments [Not Specified]
Time Frame From the first administration of study medication to the end of the 4 day residual effect period (96 hours after each administration of study medication) up to 24 days in total.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Hide Arm/Group Description The subjects received the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state. The subjects received test treatment 1 which is 10 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state. The subjects received test treatment 2 which is 50 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state. The subjects received test treatment 3 which is 500 mg metformin hydrochloride (oral solution, brand name: MetfoLiquid GeriaSan) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state. The subjects received test treatment 4 which is 1 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state. The subjects received test treatment 5 which is 5 mg furosemide (oral solution, brand name: Lasix liquidum) together with the reference treatment (REF) which is rosuvastatin (film-coated, brand name: Crestor). Trial medication was administered as a single oral dose in the fasted state.
All-Cause Mortality
REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/15 (0.00%)   0/17 (0.00%)   0/15 (0.00%)   0/15 (0.00%)   0/16 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
REF Alone Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/16 (25.00%)   4/15 (26.67%)   2/17 (11.76%)   2/15 (13.33%)   3/15 (20.00%)   2/16 (12.50%) 
Eye disorders             
Photophobia  1  0/16 (0.00%)  0/15 (0.00%)  1/17 (5.88%)  0/15 (0.00%)  0/15 (0.00%)  0/16 (0.00%) 
Gastrointestinal disorders             
Toothache  1  1/16 (6.25%)  0/15 (0.00%)  0/17 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/16 (0.00%) 
Infections and infestations             
Nasopharyngitis  1  0/16 (0.00%)  0/15 (0.00%)  0/17 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  1/16 (6.25%) 
Rhinitis  1  0/16 (0.00%)  1/15 (6.67%)  0/17 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  1/16 (6.25%) 
Injury, poisoning and procedural complications             
Contusion  1  0/16 (0.00%)  1/15 (6.67%)  0/17 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/16 (0.00%) 
Procedural pain  1  0/16 (0.00%)  0/15 (0.00%)  0/17 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/16 (0.00%)  1/15 (6.67%)  0/17 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/16 (0.00%) 
Myalgia  1  0/16 (0.00%)  1/15 (6.67%)  0/17 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/16 (0.00%) 
Nervous system disorders             
Headache  1  1/16 (6.25%)  1/15 (6.67%)  1/17 (5.88%)  1/15 (6.67%)  1/15 (6.67%)  0/16 (0.00%) 
Paraesthesia  1  1/16 (6.25%)  0/15 (0.00%)  0/17 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/16 (0.00%) 
Vascular disorders             
Haematoma  1  1/16 (6.25%)  0/15 (0.00%)  0/17 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/16 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02574845     History of Changes
Other Study ID Numbers: 352.2094
2015-003052-46 ( EudraCT Number: EudraCT )
First Submitted: October 12, 2015
First Posted: October 14, 2015
Results First Submitted: December 8, 2016
Results First Posted: February 13, 2017
Last Update Posted: February 13, 2017