Trial Outcomes & Findings for Bioequivalence Trial of Concor AM® vs Bisoprolol and Amlodipine in Chinese Participants (NCT NCT03226275)
NCT ID: NCT03226275
Last Updated: 2019-02-20
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment period
Results posted on
2019-02-20
Participant Flow
The study was designed to assess bioequivalence (BE) between a single oral dose of bisoprolol-amlodipine fixed-dose-combination (FDC) tablet and bisoprolol and amlodipine, each given concomitantly as a single dose in fasting or fed state.
Participant milestones
| Measure |
Fasting: First Bisoprolol-Amlodipine FDC, Then Both Separately
Participants received a single oral dose of 5 milligram(mg)/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 1 in treatment period 1 followed by a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 15 in treatment period 2 under fasting conditions. The two periods were separated by a washout period of 14 days.
|
Fasting: First Bisoprolol and Amlodipine Separately, Then FDC
Participants received a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 1 in treatment period 1 followed by a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 15 in treatment period 2 under fasting conditions. The two periods were separated by a washout period of 14 days.
|
Fed: First Bisoprolol-Amlodipine FDC, Then Both Separately
Participants received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 1 in treatment period 1 followed by a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 15 in treatment period 2 under fed conditions. The two periods were separated by a washout period of 14 days.
|
Fed: First Bisoprolol and Amlodipine Separately, Then FDC
Participants received a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 1 in treatment period 1 followed by a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 15 in treatment period 2 under fed conditions. The two periods were separated by a washout period of 14 days.
|
|---|---|---|---|---|
|
Treatment Period 1 (8 Days)
STARTED
|
8
|
8
|
8
|
8
|
|
Treatment Period 1 (8 Days)
COMPLETED
|
8
|
8
|
7
|
7
|
|
Treatment Period 1 (8 Days)
NOT COMPLETED
|
0
|
0
|
1
|
1
|
|
Treatment Period 2 (8 Days)
STARTED
|
8
|
8
|
7
|
7
|
|
Treatment Period 2 (8 Days)
COMPLETED
|
8
|
8
|
7
|
7
|
|
Treatment Period 2 (8 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Fasting: First Bisoprolol-Amlodipine FDC, Then Both Separately
Participants received a single oral dose of 5 milligram(mg)/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 1 in treatment period 1 followed by a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 15 in treatment period 2 under fasting conditions. The two periods were separated by a washout period of 14 days.
|
Fasting: First Bisoprolol and Amlodipine Separately, Then FDC
Participants received a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 1 in treatment period 1 followed by a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 15 in treatment period 2 under fasting conditions. The two periods were separated by a washout period of 14 days.
|
Fed: First Bisoprolol-Amlodipine FDC, Then Both Separately
Participants received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 1 in treatment period 1 followed by a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 15 in treatment period 2 under fed conditions. The two periods were separated by a washout period of 14 days.
|
Fed: First Bisoprolol and Amlodipine Separately, Then FDC
Participants received a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 1 in treatment period 1 followed by a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 15 in treatment period 2 under fed conditions. The two periods were separated by a washout period of 14 days.
|
|---|---|---|---|---|
|
Treatment Period 1 (8 Days)
Did not pass blood pressure examination
|
0
|
0
|
1
|
0
|
|
Treatment Period 1 (8 Days)
Protocol non-compliance
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Bioequivalence Trial of Concor AM® vs Bisoprolol and Amlodipine in Chinese Participants
Baseline characteristics by cohort
| Measure |
Fasting: First Bisoprolol-Amlodipine FDC, Then Both Separately
n=8 Participants
Participants received a single oral dose of 5 milligram(mg)/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 1 in treatment period 1 followed by a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 15 in treatment period 2 under fasting conditions. The two periods were separated by a washout period of 14 days.
|
Fasting: First Bisoprolol and Amlodipine Separately, Then FDC
n=8 Participants
Participants received a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 1 in treatment period 1 followed by a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 15 in treatment period 2 under fasting conditions. The two periods were separated by a washout period of 14 days.
|
Fed: First Bisoprolol-Amlodipine FDC, Then Both Separately
n=7 Participants
Participants received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 1 in treatment period 1 followed by a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 15 in treatment period 2 under fed conditions. The two periods were separated by a washout period of 14 days.
|
Fed: First Bisoprolol and Amlodipine Separately, Then FDC
n=7 Participants
Participants received a single oral dose of 5 mg bisoprolol and a single oral dose of 5 mg amlodipine given concomitantly on Day 1 in treatment period 1 followed by a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) on Day 15 in treatment period 2 under fed conditions. The two periods were separated by a washout period of 14 days.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
33.9 years
STANDARD_DEVIATION 8.89 • n=93 Participants
|
29.3 years
STANDARD_DEVIATION 3.15 • n=4 Participants
|
31.0 years
STANDARD_DEVIATION 3.56 • n=27 Participants
|
32.4 years
STANDARD_DEVIATION 10.29 • n=483 Participants
|
31.6 years
STANDARD_DEVIATION 7.01 • n=36 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
11 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
19 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
30 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic (PK) Analysis Set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect comparability of PK results, and with sufficient evaluable data to determine primary endpoints (AUC0-t and Cmax ) for both treatments.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Bisoprolol and Amlodipine
Amlodipine
|
205 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 32.1
|
212 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 34.7
|
174 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 29.9
|
167 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 33.5
|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Bisoprolol and Amlodipine
Bisoprolol
|
294 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 16.7
|
295 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 21.5
|
270 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 23.4
|
275 nanogram hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 23.9
|
PRIMARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Bisoprolol and Amlodipine
Bisoprolol
|
26.1 ng/mL
Geometric Coefficient of Variation 20.1
|
26.6 ng/mL
Geometric Coefficient of Variation 21.2
|
20.5 ng/mL
Geometric Coefficient of Variation 18.6
|
21.9 ng/mL
Geometric Coefficient of Variation 27.2
|
|
Maximum Observed Plasma Concentration (Cmax) of Bisoprolol and Amlodipine
Amlodipine
|
4.17 ng/mL
Geometric Coefficient of Variation 25.6
|
4.17 ng/mL
Geometric Coefficient of Variation 24.1
|
3.34 ng/mL
Geometric Coefficient of Variation 23.1
|
3.19 ng/mL
Geometric Coefficient of Variation 31.7
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Bisoprolol and Amlodipine
Bisoprolol
|
1.00 hours
Interval 1.0 to 3.0
|
1.00 hours
Interval 0.5 to 2.0
|
3.00 hours
Interval 1.0 to 6.0
|
3.00 hours
Interval 2.0 to 6.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Bisoprolol and Amlodipine
Amlodipine
|
6.00 hours
Interval 4.0 to 8.0
|
6.00 hours
Interval 4.0 to 12.0
|
6.00 hours
Interval 4.0 to 15.0
|
6.00 hours
Interval 4.0 to 10.0
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.
Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. Terminal half-life was calculated as ln(2)/λz, where λz is a terminal rate constant, which was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Apparent Terminal Half-life (t1/2) of Bisoprolol and Amlodipine
Bisoprolol
|
8.87 hours
Geometric Coefficient of Variation 18.1
|
8.84 hours
Geometric Coefficient of Variation 15.4
|
9.49 hours
Geometric Coefficient of Variation 30.2
|
8.86 hours
Geometric Coefficient of Variation 20.6
|
|
Apparent Terminal Half-life (t1/2) of Bisoprolol and Amlodipine
Amlodipine
|
51.8 hours
Geometric Coefficient of Variation 16.1
|
49.7 hours
Geometric Coefficient of Variation 23.5
|
46.7 hours
Geometric Coefficient of Variation 16.5
|
43.2 hours
Geometric Coefficient of Variation 26.1
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC 0-inf) of Bisoprolol and Amlodipine
Bisoprolol
|
306 ng*h/mL
Geometric Coefficient of Variation 16.6
|
306 ng*h/mL
Geometric Coefficient of Variation 21.5
|
281 ng*h/mL
Geometric Coefficient of Variation 23.4
|
287 ng*h/mL
Geometric Coefficient of Variation 23.2
|
|
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC 0-inf) of Bisoprolol and Amlodipine
Amlodipine
|
235 ng*h/mL
Geometric Coefficient of Variation 34.4
|
216 ng*h/mL
Geometric Coefficient of Variation 31.7
|
192 ng*h/mL
Geometric Coefficient of Variation 31.4
|
182 ng*h/mL
Geometric Coefficient of Variation 34.8
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set.
AUCextra% was calculated as area under the curve from time tlast extrapolated to infinity given as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Extrapolated Part of Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUCextra%) of Bisoprolol and Amlodipine
Bisoprolol
|
3.60 percentage of AUC0-inf
Geometric Coefficient of Variation 36.1
|
3.24 percentage of AUC0-inf
Geometric Coefficient of Variation 25.5
|
3.83 percentage of AUC0-inf
Geometric Coefficient of Variation 21.9
|
3.94 percentage of AUC0-inf
Geometric Coefficient of Variation 48.2
|
|
Extrapolated Part of Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUCextra%) of Bisoprolol and Amlodipine
Amlodipine
|
10.9 percentage of AUC0-inf
Geometric Coefficient of Variation 40.1
|
10.8 percentage of AUC0-inf
Geometric Coefficient of Variation 52.0
|
8.58 percentage of AUC0-inf
Geometric Coefficient of Variation 44.7
|
6.81 percentage of AUC0-inf
Geometric Coefficient of Variation 64.3
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.
λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λz) of Bisoprolol and Amlodipine
Bisoprolol
|
0.0781 1 per hour
Geometric Coefficient of Variation 18.1
|
0.0784 1 per hour
Geometric Coefficient of Variation 15.4
|
0.0731 1 per hour
Geometric Coefficient of Variation 30.2
|
0.0783 1 per hour
Geometric Coefficient of Variation 20.6
|
|
Apparent Terminal Elimination Rate Constant (λz) of Bisoprolol and Amlodipine
Amlodipine
|
0.0134 1 per hour
Geometric Coefficient of Variation 16.1
|
0.0139 1 per hour
Geometric Coefficient of Variation 23.5
|
0.0148 1 per hour
Geometric Coefficient of Variation 16.5
|
0.0160 1 per hour
Geometric Coefficient of Variation 26.1
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Apparent Total Body Clearance From Plasma (CL/f) of Bisoprolol and Amlodipine
Bisoprolol
|
16.4 liter per hour
Geometric Coefficient of Variation 16.6
|
16.4 liter per hour
Geometric Coefficient of Variation 21.5
|
17.8 liter per hour
Geometric Coefficient of Variation 23.4
|
17.4 liter per hour
Geometric Coefficient of Variation 23.2
|
|
Apparent Total Body Clearance From Plasma (CL/f) of Bisoprolol and Amlodipine
Amlodipine
|
21.3 liter per hour
Geometric Coefficient of Variation 34.4
|
23.1 liter per hour
Geometric Coefficient of Variation 31.7
|
26.0 liter per hour
Geometric Coefficient of Variation 31.4
|
27.4 liter per hour
Geometric Coefficient of Variation 34.8
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose for each treatment periodPopulation: The Pharmacokinetic analysis set. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=13 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Bisoprolol and Amlodipine
Bisoprolol
|
209 liter
Geometric Coefficient of Variation 17.0
|
209 liter
Geometric Coefficient of Variation 15.5
|
243 liter
Geometric Coefficient of Variation 31.3
|
223 liter
Geometric Coefficient of Variation 19.6
|
|
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Bisoprolol and Amlodipine
Amlodipine
|
1590 liter
Geometric Coefficient of Variation 31.0
|
1660 liter
Geometric Coefficient of Variation 40.6
|
1750 liter
Geometric Coefficient of Variation 30.9
|
1710 liter
Geometric Coefficient of Variation 40.5
|
SECONDARY outcome
Timeframe: Baseline up to Day 29Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Fasting: Bisoprolol-Amlodipine FDC
n=16 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fasting conditions.
|
Fasting: Bisoprolol and Amlodipine Separately
n=16 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fasting conditions.
|
Fed: Bisoprolol-Amlodipine FDC
n=14 Participants
All participants who received a single oral dose of 5 mg/5 mg bisoprolol-amlodipine FDC tablet as a single oral dose on Day 1 or Day 15 under fed conditions.
|
Fed: Bisoprolol and Amlodipine Separately
n=14 Participants
All participants who received a single dose of 5 mg bisoprolol and a single dose of 5 mg amlodipine given concomitantly on Day 1 or Day 15 under fed conditions.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Death, and AEs Leading to Discontinuation
TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Death, and AEs Leading to Discontinuation
Serious TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs Leading to Discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Fasting: Bisoprolol-Amlodipine FDC
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Fasting: Bisoprolol and Amlodipine Separately
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Fed: Bisoprolol-Amlodipine FDC
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Fed: Bisoprolol and Amlodipine Separately
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place