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Trial Outcomes & Findings for Bioequivalence Study Between GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Tablets and Reference Product in Healthy Adult Participants Under Fasting Conditions (NCT NCT03031496)

NCT ID: NCT03031496

Last Updated: 2021-05-07

Results Overview

Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

42 participants

Primary outcome timeframe

Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Results posted on

2021-05-07

Participant Flow

This is a Phase I, open label, balanced, randomized, single dose, two-way crossover study, enrolling 42 healthy participants at a single center in South Africa.

Total 42 participants were enrolled and randomized to receive a single oral dose of study treatment in a cross-over manner.

Participant milestones

Participant milestones
Measure
Treatment A Followed by Treatment B
Eligible participants received a single oral dose of GSK3542503 (BIDURET), hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 1. It was followed by a wash out period of 7 to 14 days. Participants received a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 2
Treatment B Followed by Treatment A
Eligible participants received a single dose of moduretic, hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 1. It was followed by a wash out period of 7 to 14 days. Participants received a single oral dose of GSK3542503 (BIDURET), hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 2.
Period 1
STARTED
21
21
Period 1
COMPLETED
19
19
Period 1
NOT COMPLETED
2
2
Period 2
STARTED
19
19
Period 2
COMPLETED
19
19
Period 2
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment A Followed by Treatment B
Eligible participants received a single oral dose of GSK3542503 (BIDURET), hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 1. It was followed by a wash out period of 7 to 14 days. Participants received a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 2
Treatment B Followed by Treatment A
Eligible participants received a single dose of moduretic, hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 1. It was followed by a wash out period of 7 to 14 days. Participants received a single oral dose of GSK3542503 (BIDURET), hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 2.
Period 1
Adverse Event
2
0
Period 1
Withdrawal by Subject
0
2

Baseline Characteristics

Bioequivalence Study Between GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Tablets and Reference Product in Healthy Adult Participants Under Fasting Conditions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Subjects
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination (either test or reference product) in each of the two treatment periods, separated by a wash out period of seven calendar days.
Age, Continuous
24.1 Years
STANDARD_DEVIATION 4.13 • n=99 Participants
Sex: Female, Male
Female
14 Participants
n=99 Participants
Sex: Female, Male
Male
28 Participants
n=99 Participants
Race/Ethnicity, Customized
Black or African American Heritage
29 Participants
n=99 Participants
Race/Ethnicity, Customized
White Heritage
12 Participants
n=99 Participants
Race/Ethnicity, Customized
Mixed Heritage
1 Participants
n=99 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Population: PK Population comprised of All participants who completed the study and for whom primary PK parameters was calculated for all treatment periods.

Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.

Outcome measures

Outcome measures
Measure
Treatment A
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride
Hydrochlorothiazide
2160 Hour x nanograms/milliliter (h*ng/mL)
Geometric Coefficient of Variation 22.0
2360 Hour x nanograms/milliliter (h*ng/mL)
Geometric Coefficient of Variation 18.8
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride
Amiloride
96.3 Hour x nanograms/milliliter (h*ng/mL)
Geometric Coefficient of Variation 22.9
94.1 Hour x nanograms/milliliter (h*ng/mL)
Geometric Coefficient of Variation 20.9

PRIMARY outcome

Timeframe: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Population: PK Population

Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.

Outcome measures

Outcome measures
Measure
Treatment A
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Hydrochlorothiazide
312 ng/mL
Geometric Coefficient of Variation 28.5
377 ng/mL
Geometric Coefficient of Variation 23.4
Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Amiloride
9.27 ng/mL
Geometric Coefficient of Variation 26.8
8.92 ng/mL
Geometric Coefficient of Variation 25.4

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Population: PK Population

Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the AUC (0-inf) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Hydrochlorothiazide; n= 37, 38
2310 h*ng/mL
Geometric Coefficient of Variation 20.8
2490 h*ng/mL
Geometric Coefficient of Variation 18.3
AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Amiloride; n= 22, 22
117 h*ng/mL
Geometric Coefficient of Variation 19.5
112 h*ng/mL
Geometric Coefficient of Variation 18.2

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Population: PK Population

Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Median and full range has been presented.

Outcome measures

Outcome measures
Measure
Treatment A
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Hydrochlorothiazide
2.505 Hour
Interval 1.01 to 4.51
1.509 Hour
Interval 0.67 to 3.5
Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Amiloride
2.507 Hour
Interval 1.5 to 4.51
2.508 Hour
Interval 1.0 to 4.51

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Population: PK Population

Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between percent AUCex of the test and reference products in relation to the conventional bioequivalence range. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Hydrochlorothiazide; n= 37, 38
5.24 Percent of area
Geometric Coefficient of Variation 37.7
4.63 Percent of area
Geometric Coefficient of Variation 33.2
Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Amiloride; n= 22, 22
9.68 Percent of area
Geometric Coefficient of Variation 35.7
10.7 Percent of area
Geometric Coefficient of Variation 44.9

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3

Population: PK Population

Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=38 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Amiloride; n= 22, 22
15.2 Hour
Interval 11.3 to 22.2
16.6 Hour
Interval 10.9 to 23.8
Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Hydrochlorothiazide; n= 37, 38
12.4 Hour
Interval 8.47 to 18.8
11.3 Hour
Interval 8.01 to 15.0

SECONDARY outcome

Timeframe: Up to 25 days

Population: Safety Population comprised of all randomized participants who received at least 1 dose of study treatment.

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Only those participants with data available at the specified time points were analyzed

Outcome measures

Outcome measures
Measure
Treatment A
n=40 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=40 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period
SAEs
0 Participants
0 Participants
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period
AEs
5 Participants
8 Participants

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Serum ALT, alk. phosph. and AST levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
Alk.phosph.; P2; Day -1; 24 hour pre-dose; n=19,19
65.1 Unit per liter (U/L)
Standard Deviation 12.52
63.6 Unit per liter (U/L)
Standard Deviation 18.27
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
Alk.phosph.; P2; Day 3; 48 hour post-dose; n=19,19
66.8 Unit per liter (U/L)
Standard Deviation 13.76
65.2 Unit per liter (U/L)
Standard Deviation 15.66
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
AST; P2; Day 3; 48 hour post-dose; n=19, 19
19.9 Unit per liter (U/L)
Standard Deviation 4.67
18.4 Unit per liter (U/L)
Standard Deviation 5.67
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
ALT; P2; Day 3; 48 hour post-dose; n= 19, 19
15.8 Unit per liter (U/L)
Standard Deviation 7.18
16.9 Unit per liter (U/L)
Standard Deviation 10.00
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
ALT;Period 1 (P1);Day -1;24 hour pre-dose;n=21,21
19.8 Unit per liter (U/L)
Standard Deviation 10.55
16.6 Unit per liter (U/L)
Standard Deviation 6.98
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
ALT; P1; Day 3; 48 hour post-dose; n= 21,20
15.9 Unit per liter (U/L)
Standard Deviation 7.92
14.1 Unit per liter (U/L)
Standard Deviation 5.49
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
ALT; P2; Day -1; 24 hour pre-dose; n= 19,19
15.8 Unit per liter (U/L)
Standard Deviation 7.03
17.6 Unit per liter (U/L)
Standard Deviation 9.08
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
Alk.phosph.; P1; Day -1; 24 hour pre-dose; n=21,21
67.5 Unit per liter (U/L)
Standard Deviation 16.59
71.1 Unit per liter (U/L)
Standard Deviation 13.20
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
Alk.phosph.; P1; Day 3; 48 hour post-dose; n=21,20
67.1 Unit per liter (U/L)
Standard Deviation 17.83
69.9 Unit per liter (U/L)
Standard Deviation 14.06
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
AST; P1; Day -1; 24 hour pre-dose; n=21, 21
21.9 Unit per liter (U/L)
Standard Deviation 8.56
20.1 Unit per liter (U/L)
Standard Deviation 4.43
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
AST; P1; Day 3; 48 hour post-dose; n=21, 20
17.5 Unit per liter (U/L)
Standard Deviation 4.26
17.8 Unit per liter (U/L)
Standard Deviation 3.81
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
AST; P2; Day -1; 24 hour pre-dose; n=19, 19
21.6 Unit per liter (U/L)
Standard Deviation 5.81
21.1 Unit per liter (U/L)
Standard Deviation 5.66

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Serum BUN levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
P1; Day-1; 24 hour pre-dose; n=21, 21
12.519 Milligrams per deciliter (mg/dL)
Standard Deviation 3.327
12.702 Milligrams per deciliter (mg/dL)
Standard Deviation 3.954
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
P2; Day -1; 24 hour pre-dose; n=19, 19
12.185 Milligrams per deciliter (mg/dL)
Standard Deviation 2.345
12.164 Milligrams per deciliter (mg/dL)
Standard Deviation 3.216
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
P1; Day 3; 48 hour post-dose; n=21, 20
14.970 Milligrams per deciliter (mg/dL)
Standard Deviation 3.626
15.593 Milligrams per deciliter (mg/dL)
Standard Deviation 3.020
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
P2; Day 3; 48 hour post-dose; n=19, 19
16.372 Milligrams per deciliter (mg/dL)
Standard Deviation 4.446
15.208 Milligrams per deciliter (mg/dL)
Standard Deviation 3.493

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Serum calcium, chloride, glucose, magnesium, potassium and sodium levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Chloride; P1; Day 3; 48 hour post-dose; n= 21, 20
103.27 Millimoles per liter (Mmol/L)
Standard Deviation 1.755
102.63 Millimoles per liter (Mmol/L)
Standard Deviation 2.011
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Chloride; P2; Day-1; 24 hour pre-dose; n= 19, 19
104.36 Millimoles per liter (Mmol/L)
Standard Deviation 1.729
104.85 Millimoles per liter (Mmol/L)
Standard Deviation 2.252
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Sodium; P2; Day 3; 48 hour post-dose; n= 19, 19
139.11 Millimoles per liter (Mmol/L)
Standard Deviation 1.761
139.11 Millimoles per liter (Mmol/L)
Standard Deviation 2.424
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Glucose; P1; Day-1; 24 hour pre-dose; n= 21, 20
4.746 Millimoles per liter (Mmol/L)
Standard Deviation 0.777
4.643 Millimoles per liter (Mmol/L)
Standard Deviation 0.427
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Glucose; P1; Day 3; 48 hour post-dose; n= 21, 20
5.006 Millimoles per liter (Mmol/L)
Standard Deviation 0.597
4.827 Millimoles per liter (Mmol/L)
Standard Deviation 0.368
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Magnesium; P1; Day-1; 24 hour pre-dose; n= 21, 21
0.782 Millimoles per liter (Mmol/L)
Standard Deviation 0.066
0.801 Millimoles per liter (Mmol/L)
Standard Deviation 0.049
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Magnesium; P1; Day 3; 48 hour post-dose; n= 21, 20
0.781 Millimoles per liter (Mmol/L)
Standard Deviation 0.039
0.804 Millimoles per liter (Mmol/L)
Standard Deviation 0.044
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Magnesium; P2; Day-1; 24 hour pre-dose; n= 19, 19
0.826 Millimoles per liter (Mmol/L)
Standard Deviation 0.053
0.805 Millimoles per liter (Mmol/L)
Standard Deviation 0.053
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Magnesium; P2; Day 3; 48 hour post-dose; n= 19, 19
0.821 Millimoles per liter (Mmol/L)
Standard Deviation 0.051
0.783 Millimoles per liter (Mmol/L)
Standard Deviation 0.052
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Potassium; P2; Day 3; 48 hour post-dose; n= 19, 19
4.364 Millimoles per liter (Mmol/L)
Standard Deviation 0.303
4.336 Millimoles per liter (Mmol/L)
Standard Deviation 0.288
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Potassium; P1; Day-1; 24 hour pre-dose; n= 21, 21
4.287 Millimoles per liter (Mmol/L)
Standard Deviation 0.347
4.294 Millimoles per liter (Mmol/L)
Standard Deviation 0.390
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Potassium; P1; Day 3; 48 hour post-dose; n= 21, 20
4.303 Millimoles per liter (Mmol/L)
Standard Deviation 0.346
4.222 Millimoles per liter (Mmol/L)
Standard Deviation 0.438
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Potassium; P2; Day-1; 24 hour pre-dose; n= 19, 19
4.300 Millimoles per liter (Mmol/L)
Standard Deviation 0.374
4.225 Millimoles per liter (Mmol/L)
Standard Deviation 0.289
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Sodium; P1; Day-1; 24 hour pre-dose; n= 21, 21
140.86 Millimoles per liter (Mmol/L)
Standard Deviation 2.242
140.67 Millimoles per liter (Mmol/L)
Standard Deviation 1.958
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Sodium; P1; Day 3; 48 hour post-dose; n= 21, 20
138.90 Millimoles per liter (Mmol/L)
Standard Deviation 1.480
139.25 Millimoles per liter (Mmol/L)
Standard Deviation 1.410
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Sodium; P2; Day-1; 24 hour pre-dose; n= 19, 19
140.11 Millimoles per liter (Mmol/L)
Standard Deviation 1.410
139.68 Millimoles per liter (Mmol/L)
Standard Deviation 2.187
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Calcium; P1; Day-1; 24 hour pre-dose; n= 21, 21
2.400 Millimoles per liter (Mmol/L)
Standard Deviation 0.075
2.418 Millimoles per liter (Mmol/L)
Standard Deviation 0.085
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Calcium; P1; Day 3; 48 hour post-dose; n= 21, 20
2.396 Millimoles per liter (Mmol/L)
Standard Deviation 0.078
2.393 Millimoles per liter (Mmol/L)
Standard Deviation 0.071
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Calcium; P2; Day-1; 24 hour pre-dose; n= 19, 19
2.374 Millimoles per liter (Mmol/L)
Standard Deviation 0.053
2.335 Millimoles per liter (Mmol/L)
Standard Deviation 0.074
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Calcium; P2; Day 3; 48 hour post-dose; n= 19, 19
2.415 Millimoles per liter (Mmol/L)
Standard Deviation 0.078
2.379 Millimoles per liter (Mmol/L)
Standard Deviation 0.069
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Chloride; P1; Day-1; 24 hour pre-dose; n= 21, 21
104.80 Millimoles per liter (Mmol/L)
Standard Deviation 2.286
103.62 Millimoles per liter (Mmol/L)
Standard Deviation 2.225
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Chloride; P2; Day 3; 48 hour post-dose; n= 19, 19
102.62 Millimoles per liter (Mmol/L)
Standard Deviation 1.985
103.49 Millimoles per liter (Mmol/L)
Standard Deviation 1.882
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Glucose; P2; Day-1; 24 hour pre-dose; n= 19, 19
4.754 Millimoles per liter (Mmol/L)
Standard Deviation 0.316
4.765 Millimoles per liter (Mmol/L)
Standard Deviation 0.354
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Glucose; P2; Day 3; 48 hour post-dose; n= 19, 19
4.652 Millimoles per liter (Mmol/L)
Standard Deviation 0.357
4.732 Millimoles per liter (Mmol/L)
Standard Deviation 0.282

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Serum creatinine, direct bilirubin and total bilirubin levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Creatinine; P1; Day-1; 24 hour pre-dose; n= 21, 21
85.2 Micromoles per liter (µmol/L)
Standard Deviation 13.69
85.0 Micromoles per liter (µmol/L)
Standard Deviation 11.51
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Creatinine; P1; Day3; 48 hour post-dose; n= 21, 20
87.0 Micromoles per liter (µmol/L)
Standard Deviation 15.26
87.3 Micromoles per liter (µmol/L)
Standard Deviation 12.18
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Creatinine; P2; Day-1; 24 hour pre-dose; n= 19, 19
82.1 Micromoles per liter (µmol/L)
Standard Deviation 10.99
82.5 Micromoles per liter (µmol/L)
Standard Deviation 13.33
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Creatinine; P2; Day3; 48 hour post-dose; n= 19, 19
85.6 Micromoles per liter (µmol/L)
Standard Deviation 15.31
88.7 Micromoles per liter (µmol/L)
Standard Deviation 16.69
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Direct bilirubin;P1;Day3;48 hour post-dose;n=21,20
3.20 Micromoles per liter (µmol/L)
Standard Deviation 1.599
3.72 Micromoles per liter (µmol/L)
Standard Deviation 1.493
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Direct bilirubin;P2;Day3;48 hour post-dose;n=19,19
3.77 Micromoles per liter (µmol/L)
Standard Deviation 1.559
3.14 Micromoles per liter (µmol/L)
Standard Deviation 1.340
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Total bilirubin;P2;Day3;48 hour post-dose;n=19,19
10.83 Micromoles per liter (µmol/L)
Standard Deviation 5.920
8.67 Micromoles per liter (µmol/L)
Standard Deviation 4.492
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Direct bilirubin;P1;Day-1;24 hour pre-dose;n=21,21
4.25 Micromoles per liter (µmol/L)
Standard Deviation 1.771
4.52 Micromoles per liter (µmol/L)
Standard Deviation 1.825
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Direct bilirubin;P2;Day-1;24 hour pre-dose;n=19,19
3.94 Micromoles per liter (µmol/L)
Standard Deviation 1.357
3.64 Micromoles per liter (µmol/L)
Standard Deviation 1.446
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Total bilirubin;P1;Day-1;24 hour pre-dose;n=21,21
12.10 Micromoles per liter (µmol/L)
Standard Deviation 6.208
13.48 Micromoles per liter (µmol/L)
Standard Deviation 6.923
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Total bilirubin;P1;Day3;48 hour post-dose;n=21,20
9.40 Micromoles per liter (µmol/L)
Standard Deviation 5.265
10.80 Micromoles per liter (µmol/L)
Standard Deviation 5.601
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Total bilirubin;P2;Day-1;24 hour pre-dose;n=19,19
10.61 Micromoles per liter (µmol/L)
Standard Deviation 4.651
10.08 Micromoles per liter (µmol/L)
Standard Deviation 5.119

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Serum total protein levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Total Protein Levels at Indicated Time Points
P1; Day-1; 24 hours pre-dose; n= 21, 21
74.08 Grams per liter (g/L)
Standard Deviation 4.943
76.06 Grams per liter (g/L)
Standard Deviation 3.733
Total Protein Levels at Indicated Time Points
P2; Day 3; 48 hours post-dose; n= 19, 19
73.56 Grams per liter (g/L)
Standard Deviation 3.676
72.33 Grams per liter (g/L)
Standard Deviation 4.241
Total Protein Levels at Indicated Time Points
P1; Day 3; 48 hours post-dose; n= 21, 20
74.53 Grams per liter (g/L)
Standard Deviation 5.259
74.99 Grams per liter (g/L)
Standard Deviation 3.844
Total Protein Levels at Indicated Time Points
P2; Day-1; 24 hours pre-dose; n= 19, 19
71.29 Grams per liter (g/L)
Standard Deviation 3.369
70.06 Grams per liter (g/L)
Standard Deviation 4.002

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day1; 2 hour post-dose; n= 21, 21
113.3 Millimeters of mercury (mmHg)
Standard Deviation 9.59
112.6 Millimeters of mercury (mmHg)
Standard Deviation 7.95
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP: P1; Day1; 4 hour post-dose; n= 21, 21
112.5 Millimeters of mercury (mmHg)
Standard Deviation 8.66
114.0 Millimeters of mercury (mmHg)
Standard Deviation 9.30
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day3; 48 hour post-dose; n= 21, 20
114.5 Millimeters of mercury (mmHg)
Standard Deviation 9.11
113.8 Millimeters of mercury (mmHg)
Standard Deviation 9.20
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P2; Day1; 1.5 hour post-dose; n= 19, 19
108.9 Millimeters of mercury (mmHg)
Standard Deviation 8.14
112.2 Millimeters of mercury (mmHg)
Standard Deviation 12.62
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP: P2; Day2; 24 hour post-dose; n= 19, 19
109.1 Millimeters of mercury (mmHg)
Standard Deviation 7.13
110.6 Millimeters of mercury (mmHg)
Standard Deviation 10.03
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P1; Day-1; 12 hour pre-dose; n= 21, 21
65.4 Millimeters of mercury (mmHg)
Standard Deviation 7.32
64.9 Millimeters of mercury (mmHg)
Standard Deviation 7.25
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P1; Day1; 1 hour post-dose; n= 21, 21
63.7 Millimeters of mercury (mmHg)
Standard Deviation 6.79
63.5 Millimeters of mercury (mmHg)
Standard Deviation 5.55
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P1; Day1; 4 hour post-dose; n= 21, 21
64.8 Millimeters of mercury (mmHg)
Standard Deviation 6.82
64.4 Millimeters of mercury (mmHg)
Standard Deviation 7.21
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P1; Day1; 6 hour post-dose; n= 21, 21
61.4 Millimeters of mercury (mmHg)
Standard Deviation 4.34
62.7 Millimeters of mercury (mmHg)
Standard Deviation 6.20
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P1; Day1; 8 hour post-dose; n= 21, 21
63.0 Millimeters of mercury (mmHg)
Standard Deviation 6.00
63.7 Millimeters of mercury (mmHg)
Standard Deviation 6.02
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P1; Day2; 24 hour post-dose; n= 21, 21
64.9 Millimeters of mercury (mmHg)
Standard Deviation 5.06
64.2 Millimeters of mercury (mmHg)
Standard Deviation 5.86
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P1; Day3; 48 hour post-dose; n= 21, 20
67.3 Millimeters of mercury (mmHg)
Standard Deviation 5.55
66.0 Millimeters of mercury (mmHg)
Standard Deviation 6.38
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P2; Day-1; 12 hour post-dose; n= 19, 19
63.1 Millimeters of mercury (mmHg)
Standard Deviation 6.03
65.8 Millimeters of mercury (mmHg)
Standard Deviation 7.65
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P2; Day1; 1 hour post-dose; n= 19, 19
63.9 Millimeters of mercury (mmHg)
Standard Deviation 6.86
64.1 Millimeters of mercury (mmHg)
Standard Deviation 8.39
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P2; Day1; 1.5 hour post-dose; n= 19, 19
61.1 Millimeters of mercury (mmHg)
Standard Deviation 5.36
63.4 Millimeters of mercury (mmHg)
Standard Deviation 8.64
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P2; Day1; 2 hour post-dose; n= 19, 19
62.5 Millimeters of mercury (mmHg)
Standard Deviation 6.87
65.3 Millimeters of mercury (mmHg)
Standard Deviation 7.28
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P2; Day1; 4 hour post-dose; n= 19, 19
62.8 Millimeters of mercury (mmHg)
Standard Deviation 7.73
65.3 Millimeters of mercury (mmHg)
Standard Deviation 8.08
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P2; Day1; 6 hour post-dose; n= 19, 19
59.4 Millimeters of mercury (mmHg)
Standard Deviation 5.85
61.5 Millimeters of mercury (mmHg)
Standard Deviation 6.33
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P2; Day1; 8 hour post-dose; n= 19, 19
61.1 Millimeters of mercury (mmHg)
Standard Deviation 5.91
62.9 Millimeters of mercury (mmHg)
Standard Deviation 6.75
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P2; Day3; 48 hour post-dose; n= 18, 19
65.9 Millimeters of mercury (mmHg)
Standard Deviation 7.28
67.2 Millimeters of mercury (mmHg)
Standard Deviation 6.64
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day-1; 12 hour pre-dose; n=21,21
115.9 Millimeters of mercury (mmHg)
Standard Deviation 6.88
115.8 Millimeters of mercury (mmHg)
Standard Deviation 8.99
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day1; 1 hour post-dose; n= 21, 21
112.8 Millimeters of mercury (mmHg)
Standard Deviation 8.90
111.6 Millimeters of mercury (mmHg)
Standard Deviation 7.56
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day1; 1.5 hour pre-dose; n= 21, 21
111.5 Millimeters of mercury (mmHg)
Standard Deviation 8.15
110.8 Millimeters of mercury (mmHg)
Standard Deviation 11.01
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day1; 6 hour post-dose; n= 21, 21
110.9 Millimeters of mercury (mmHg)
Standard Deviation 6.69
113.0 Millimeters of mercury (mmHg)
Standard Deviation 8.26
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day1; 8 hour post-dose; n= 21, 21
113.0 Millimeters of mercury (mmHg)
Standard Deviation 8.66
111.8 Millimeters of mercury (mmHg)
Standard Deviation 8.62
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P1; Day2; 24 hour post-dose; n= 21, 21
111.4 Millimeters of mercury (mmHg)
Standard Deviation 6.99
110.5 Millimeters of mercury (mmHg)
Standard Deviation 6.79
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P2; Day-1; 12 hour pre-dose; n= 19, 19
113.8 Millimeters of mercury (mmHg)
Standard Deviation 7.38
116.2 Millimeters of mercury (mmHg)
Standard Deviation 10.04
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P2; Day1; 1 hour post-dose; n= 19, 19
110.0 Millimeters of mercury (mmHg)
Standard Deviation 8.54
113.7 Millimeters of mercury (mmHg)
Standard Deviation 11.71
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P2; Day1; 2 hour post-dose; n= 19, 19
109.6 Millimeters of mercury (mmHg)
Standard Deviation 7.73
113.8 Millimeters of mercury (mmHg)
Standard Deviation 12.49
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP: P2; Day1; 4 hour post-dose; n= 19, 19
109.5 Millimeters of mercury (mmHg)
Standard Deviation 9.54
113.5 Millimeters of mercury (mmHg)
Standard Deviation 11.57
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP: P2; Day1; 6 hour post-dose; n= 19, 19
108.5 Millimeters of mercury (mmHg)
Standard Deviation 7.57
112.4 Millimeters of mercury (mmHg)
Standard Deviation 10.79
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP: P2; Day1; 8 hour post-dose; n= 19, 19
109.8 Millimeters of mercury (mmHg)
Standard Deviation 8.53
111.5 Millimeters of mercury (mmHg)
Standard Deviation 12.04
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
SBP; P2; Day3; 48 hour post-dose; n= 18, 19
112.9 Millimeters of mercury (mmHg)
Standard Deviation 8.56
116.5 Millimeters of mercury (mmHg)
Standard Deviation 9.18
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P1; Day1; 1.5 hour post-dose; n= 21, 21
64.0 Millimeters of mercury (mmHg)
Standard Deviation 7.08
63.9 Millimeters of mercury (mmHg)
Standard Deviation 8.57
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP; P1; Day1; 2 hour post-dose; n= 21, 21
63.4 Millimeters of mercury (mmHg)
Standard Deviation 7.10
65.7 Millimeters of mercury (mmHg)
Standard Deviation 9.45
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
DBP: P2; Day2; 24 hour post-dose; n= 19, 19
62.9 Millimeters of mercury (mmHg)
Standard Deviation 5.62
64.4 Millimeters of mercury (mmHg)
Standard Deviation 7.79

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Vital sign measurements including respiratory rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Respiratory Rate Values at Indicated Time Points
P1; Day1; 2 hour post-dose; n= 21, 21
17.0 Breaths per minute
Standard Deviation 2.06
17.5 Breaths per minute
Standard Deviation 2.36
Respiratory Rate Values at Indicated Time Points
P2; Day-1; 12 hour pre-dose; n= 19, 19
17.9 Breaths per minute
Standard Deviation 1.47
17.2 Breaths per minute
Standard Deviation 1.54
Respiratory Rate Values at Indicated Time Points
P2; Day1; 1 hour post-dose; n= 19, 19
17.7 Breaths per minute
Standard Deviation 2.03
17.9 Breaths per minute
Standard Deviation 1.56
Respiratory Rate Values at Indicated Time Points
P2; Day1; 1.5 hour post-dose; n= 19, 19
15.8 Breaths per minute
Standard Deviation 1.65
16.3 Breaths per minute
Standard Deviation 1.82
Respiratory Rate Values at Indicated Time Points
P2; Day1; 2 hour post-dose; n= 19, 19
18.0 Breaths per minute
Standard Deviation 1.89
17.3 Breaths per minute
Standard Deviation 2.84
Respiratory Rate Values at Indicated Time Points
P2; Day1; 4 hour post-dose; n= 19, 19
17.9 Breaths per minute
Standard Deviation 2.26
17.4 Breaths per minute
Standard Deviation 2.50
Respiratory Rate Values at Indicated Time Points
P2; Day1; 6 hour post-dose; n= 19, 19
17.2 Breaths per minute
Standard Deviation 1.92
18.3 Breaths per minute
Standard Deviation 2.52
Respiratory Rate Values at Indicated Time Points
P2; Day3; 48 hour post-dose; n= 18, 19
18.4 Breaths per minute
Standard Deviation 1.62
17.2 Breaths per minute
Standard Deviation 2.42
Respiratory Rate Values at Indicated Time Points
P1; Day-1; 12 hour pre-dose; n= 21, 21
16.5 Breaths per minute
Standard Deviation 1.63
17.0 Breaths per minute
Standard Deviation 1.45
Respiratory Rate Values at Indicated Time Points
P1; Day1; 1 hour post-dose; n= 21, 21
16.3 Breaths per minute
Standard Deviation 2.70
17.0 Breaths per minute
Standard Deviation 2.33
Respiratory Rate Values at Indicated Time Points
P1; Day1; 1.5 hour post-dose; n= 21, 21
16.7 Breaths per minute
Standard Deviation 1.91
17.9 Breaths per minute
Standard Deviation 1.62
Respiratory Rate Values at Indicated Time Points
P1; Day1; 4 hour post-dose; n= 21, 21
16.9 Breaths per minute
Standard Deviation 2.49
17.0 Breaths per minute
Standard Deviation 2.25
Respiratory Rate Values at Indicated Time Points
P1; Day1; 6 hour post-dose; n= 21, 21
17.2 Breaths per minute
Standard Deviation 2.49
18.4 Breaths per minute
Standard Deviation 2.16
Respiratory Rate Values at Indicated Time Points
P1; Day1; 8 hour post-dose; n= 21, 21
16.9 Breaths per minute
Standard Deviation 2.24
18.2 Breaths per minute
Standard Deviation 1.89
Respiratory Rate Values at Indicated Time Points
P1; Day2; 24 hour post-dose; n= 21, 21
18.2 Breaths per minute
Standard Deviation 1.41
18.0 Breaths per minute
Standard Deviation 1.80
Respiratory Rate Values at Indicated Time Points
P1; Day3; 48 hour post-dose; n= 21, 20
17.1 Breaths per minute
Standard Deviation 1.53
17.7 Breaths per minute
Standard Deviation 1.89
Respiratory Rate Values at Indicated Time Points
P2; Day1; 8 hour post-dose; n= 19, 19
18.7 Breaths per minute
Standard Deviation 1.52
18.2 Breaths per minute
Standard Deviation 2.10
Respiratory Rate Values at Indicated Time Points
P2; Day2; 24 hour post-dose; n= 19, 19
17.5 Breaths per minute
Standard Deviation 2.72
17.6 Breaths per minute
Standard Deviation 1.64

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Pulse Rate Values at Indicated Time Points
P1; Day1; 2 hour post-dose; n= 21, 21
61.7 Beats per minute (bpm)
Standard Deviation 10.55
60.7 Beats per minute (bpm)
Standard Deviation 8.97
Pulse Rate Values at Indicated Time Points
P1; Day-1; 12 hour pre-dose; n= 21, 21
66.9 Beats per minute (bpm)
Standard Deviation 9.22
64.7 Beats per minute (bpm)
Standard Deviation 9.57
Pulse Rate Values at Indicated Time Points
P1; Day1; 4 hour post-dose; n= 21, 21
64.1 Beats per minute (bpm)
Standard Deviation 11.32
62.5 Beats per minute (bpm)
Standard Deviation 9.91
Pulse Rate Values at Indicated Time Points
P1; Day1; 6 hour post-dose; n= 21, 21
71.5 Beats per minute (bpm)
Standard Deviation 13.85
70.8 Beats per minute (bpm)
Standard Deviation 10.17
Pulse Rate Values at Indicated Time Points
P1; Day2; 24 hour post-dose; n= 21, 21
69.0 Beats per minute (bpm)
Standard Deviation 11.26
68.6 Beats per minute (bpm)
Standard Deviation 10.18
Pulse Rate Values at Indicated Time Points
P1; Day3; 48 hour post-dose; n= 21, 20
71.4 Beats per minute (bpm)
Standard Deviation 12.93
73.0 Beats per minute (bpm)
Standard Deviation 9.49
Pulse Rate Values at Indicated Time Points
P2; Day-1; 12 hour pre-dose; n= 19, 19
65.2 Beats per minute (bpm)
Standard Deviation 9.15
65.2 Beats per minute (bpm)
Standard Deviation 11.95
Pulse Rate Values at Indicated Time Points
P2; Day1; 6 hour post-dose; n= 19, 19
72.9 Beats per minute (bpm)
Standard Deviation 8.23
71.4 Beats per minute (bpm)
Standard Deviation 13.25
Pulse Rate Values at Indicated Time Points
P2; Day2; 24 hour post-dose; n= 19, 19
69.0 Beats per minute (bpm)
Standard Deviation 9.99
68.8 Beats per minute (bpm)
Standard Deviation 13.29
Pulse Rate Values at Indicated Time Points
P2; Day3; 48 hour post-dose; n= 18, 19
70.3 Beats per minute (bpm)
Standard Deviation 11.69
73.4 Beats per minute (bpm)
Standard Deviation 17.13
Pulse Rate Values at Indicated Time Points
P1; Day1; 1 hour post-dose; n= 21, 21
61.8 Beats per minute (bpm)
Standard Deviation 11.26
62.0 Beats per minute (bpm)
Standard Deviation 10.26
Pulse Rate Values at Indicated Time Points
P1; Day1; 1.5 hour post-dose; n= 21, 21
62.5 Beats per minute (bpm)
Standard Deviation 10.95
60.9 Beats per minute (bpm)
Standard Deviation 11.05
Pulse Rate Values at Indicated Time Points
P1; Day1; 8 hour post-dose; n= 21, 21
66.0 Beats per minute (bpm)
Standard Deviation 9.93
67.8 Beats per minute (bpm)
Standard Deviation 9.33
Pulse Rate Values at Indicated Time Points
P2; Day1; 1 hour post-dose; n= 19, 19
62.5 Beats per minute (bpm)
Standard Deviation 8.82
60.1 Beats per minute (bpm)
Standard Deviation 9.72
Pulse Rate Values at Indicated Time Points
P2; Day1; 1.5 hour post-dose; n= 19, 19
61.5 Beats per minute (bpm)
Standard Deviation 8.02
62.8 Beats per minute (bpm)
Standard Deviation 10.97
Pulse Rate Values at Indicated Time Points
P2; Day1; 2 hour post-dose; n= 19, 19
60.7 Beats per minute (bpm)
Standard Deviation 8.33
59.2 Beats per minute (bpm)
Standard Deviation 8.60
Pulse Rate Values at Indicated Time Points
P2; Day1; 4 hour post-dose; n= 19, 19
62.4 Beats per minute (bpm)
Standard Deviation 8.58
62.7 Beats per minute (bpm)
Standard Deviation 11.36
Pulse Rate Values at Indicated Time Points
P2; Day1; 8 hour post-dose; n= 19, 19
68.2 Beats per minute (bpm)
Standard Deviation 8.89
66.2 Beats per minute (bpm)
Standard Deviation 11.26

SECONDARY outcome

Timeframe: Day -1 and Day 3 of each treatment period

Population: Safety Population

Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Outcome measures

Outcome measures
Measure
Treatment A
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=42 Participants
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Body Temperature Values at Indicated Time Points
P1; Day-1; 12 hour pre-dose; n= 21, 21
36.42 Degree Celsius
Standard Deviation 0.339
36.43 Degree Celsius
Standard Deviation 0.376
Body Temperature Values at Indicated Time Points
P1; Day1; 1 hour post-dose; n= 21, 21
36.44 Degree Celsius
Standard Deviation 0.262
36.40 Degree Celsius
Standard Deviation 0.392
Body Temperature Values at Indicated Time Points
P1; Day1; 1.5 hour post-dose; n= 21, 21
36.06 Degree Celsius
Standard Deviation 0.294
36.05 Degree Celsius
Standard Deviation 0.314
Body Temperature Values at Indicated Time Points
P1; Day1; 2 hour post-dose; n= 21, 21
36.42 Degree Celsius
Standard Deviation 0.339
36.38 Degree Celsius
Standard Deviation 0.314
Body Temperature Values at Indicated Time Points
P1; Day1; 4 hour post-dose; n= 21, 21
36.45 Degree Celsius
Standard Deviation 0.364
36.46 Degree Celsius
Standard Deviation 0.365
Body Temperature Values at Indicated Time Points
P1; Day1; 6 hour post-dose; n= 21, 21
36.59 Degree Celsius
Standard Deviation 0.422
36.61 Degree Celsius
Standard Deviation 0.309
Body Temperature Values at Indicated Time Points
P1; Day1; 8 hour post-dose; n= 21, 21
36.64 Degree Celsius
Standard Deviation 0.461
36.75 Degree Celsius
Standard Deviation 0.357
Body Temperature Values at Indicated Time Points
P1; Day2; 24 hour post-dose; n= 21, 21
36.28 Degree Celsius
Standard Deviation 0.387
36.30 Degree Celsius
Standard Deviation 0.322
Body Temperature Values at Indicated Time Points
P1; Day3; 48 hour post-dose; n= 21, 20
36.26 Degree Celsius
Standard Deviation 0.334
36.28 Degree Celsius
Standard Deviation 0.374
Body Temperature Values at Indicated Time Points
P2; Day-1; 12 hour pre-dose; n= 19, 19
36.41 Degree Celsius
Standard Deviation 0.358
36.34 Degree Celsius
Standard Deviation 0.383
Body Temperature Values at Indicated Time Points
P2; Day1; 1 hour post-dose; n= 19, 19
36.28 Degree Celsius
Standard Deviation 0.302
36.24 Degree Celsius
Standard Deviation 0.435
Body Temperature Values at Indicated Time Points
P2; Day1; 1.5 hour post-dose; n= 19, 19
36.06 Degree Celsius
Standard Deviation 0.263
36.19 Degree Celsius
Standard Deviation 0.336
Body Temperature Values at Indicated Time Points
P2; Day1; 2 hour post-dose; n= 19, 19
36.41 Degree Celsius
Standard Deviation 0.294
36.38 Degree Celsius
Standard Deviation 0.405
Body Temperature Values at Indicated Time Points
P2; Day1; 4 hour post-dose; n= 19, 19
36.53 Degree Celsius
Standard Deviation 0.335
36.44 Degree Celsius
Standard Deviation 0.380
Body Temperature Values at Indicated Time Points
P2; Day1; 6 hour post-dose; n= 19, 19
36.59 Degree Celsius
Standard Deviation 0.331
36.57 Degree Celsius
Standard Deviation 0.406
Body Temperature Values at Indicated Time Points
P2; Day1; 8 hour post-dose; n= 19, 19
36.64 Degree Celsius
Standard Deviation 0.383
36.65 Degree Celsius
Standard Deviation 0.399
Body Temperature Values at Indicated Time Points
P2; Day2; 24 hour post-dose; n= 19, 19
36.15 Degree Celsius
Standard Deviation 0.301
36.17 Degree Celsius
Standard Deviation 0.437
Body Temperature Values at Indicated Time Points
P2; Day3; 48 hour post-dose; n= 18, 19
36.08 Degree Celsius
Standard Deviation 0.323
36.28 Degree Celsius
Standard Deviation 0.486

Adverse Events

Treatment A

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Treatment B

Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Treatment A
n=40 participants at risk
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.
Treatment B
n=40 participants at risk
Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods
Ear and labyrinth disorders
Ear Pain
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
2.5%
1/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Gastrointestinal disorders
Abdominal Pain
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
5.0%
2/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Gastrointestinal disorders
Diarrhoea
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
2.5%
1/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Investigations
Crystal Urine
2.5%
1/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders
Hyperkalaemia
2.5%
1/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Nervous system disorders
Dizziness
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
12.5%
5/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Nervous system disorders
Headache
7.5%
3/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
7.5%
3/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.00%
0/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.
2.5%
1/40 • On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).
On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

  • Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER