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

An Open-label, Randomized, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Fixed Dose Combination Tablets Versus Reference Product in Healthy Adult Participants Under Fasting Conditions

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03031496

Enrollment

Registered

2017-01-25

Start date

2017-03-17

Completion date

2017-04-10

Last updated

2021-05-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension

Keywords

Cross-over, Hydrochlorothiazide, Amiloride hydrochloride, Phase I, GSK3542503, Bioequivalence, FTIH

Brief summary

The combination of the diuretics amiloride hydrochloride (HCl) and hydrochlorothiazide (HCTZ) (GSK3542503) is indicated for the treatment of hypertension, congestive heart failure and hepatic cirrhosis with ascites and edema. This first time in human (FTIH) study is aimed to determine whether the test product GSK3542503 is bioequivalent to the reference (ref) hydrochlorothiazide 50 milligram (mg)/amiloride hydrochlorothiazide 5 mg in healthy adult participants under fasting conditions based on pharmacokinetic (PK) endpoints. This is a phase I, open label, balanced, randomized, single dose, two-way crossover study, enroling approximately 42 healthy participants at a single center. Study participants will be randomized to one of two treatment sequences (A-B or B-A) in accordance with the randomization schedule. A single dose of one of the two treatments A (Test: GSK3542503, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination) or B (Reference: Moduretic, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination), will be administered on Day 1, in each treatment period. Each participant will participate in both treatment periods and receive a single dose of each treatment. The treatment periods will be separated by a washout period of at least 7 days and no more than 14 days. The total duration in the study for each participant is expected to be 5 to 7 weeks, from screening to his or her last visit. A maximum of 42 participants will be randomized such that at least 32 evaluable participants complete the study.

Interventions

DRUGGSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets)

GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) are cream-colored, circular, flat faced uncoated tablets with beveled edges having break line on one side and BD embossed on the other side.

DRUGModuretic (HCTZ 50mg/Amiloride HCl 5mg tablets)

Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) tablets are peach-colored, half scored, diamond shaped tablets marked MSD917.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

* Participants must be between18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or

Exclusion criteria

, outside the normal reference range for the population being studied may be included only if the investigator in consultation with the medical monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg/meter\^2(inclusive). * Healthy male or female participants * Male participants must agree to use contraception for 3 days after each dose of study treatment and refrain from donating sperm during that period. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment. The investigator is responsible for ensuring that male and female study participants understand how to correctly use the methods of contraception. \- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions.

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride	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	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.
Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	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	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.

Secondary

Measure	Time frame	Description
Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	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	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).
Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	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	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).
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period	Up to 25 days	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
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	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	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).
Total Protein Levels at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Respiratory Rate Values at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Pulse Rate Values at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Body Temperature Values at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Day -1 and Day 3 of each treatment period	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).
Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	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	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.

Countries

South Africa

Participant flow

Recruitment details

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.

Pre-assignment details

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

Participants by arm

Arm	Count
All Subjects 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.	42
Total	42

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period 1	Adverse Event	2	0
Period 1	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	All Subjects
Age, Continuous	24.1 Years STANDARD_DEVIATION 4.13
Race/Ethnicity, Customized Black or African American Heritage	29 Participants
Race/Ethnicity, Customized Mixed Heritage	1 Participants
Race/Ethnicity, Customized White Heritage	12 Participants
Sex: Female, Male Female	14 Participants
Sex: Female, Male Male	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 40	0 / 40
other Total, other adverse events	5 / 40	13 / 40
serious Total, serious adverse events	0 / 40	0 / 40

Outcome results

Primary

Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment B	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	2360 Hour x nanograms/milliliter (h*ng/mL)	Geometric Coefficient of Variation 18.8
Treatment B	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	94.1 Hour x nanograms/milliliter (h*ng/mL)	Geometric Coefficient of Variation 20.9

90% CI: [87.77, 95.43]

90% CI: [98.12, 106.91]

Primary

Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

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.

Population: PK Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide	312 ng/mL	Geometric Coefficient of Variation 28.5
Treatment A	Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride	9.27 ng/mL	Geometric Coefficient of Variation 26.8
Treatment B	Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide	377 ng/mL	Geometric Coefficient of Variation 23.4
Treatment B	Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride	8.92 ng/mL	Geometric Coefficient of Variation 25.4

90% CI: [77.37, 88.74]

90% CI: [97.42, 110.86]

Secondary

Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment B	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	18.4 Unit per liter (U/L)	Standard Deviation 5.67
Treatment B	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	16.6 Unit per liter (U/L)	Standard Deviation 6.98
Treatment B	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	17.6 Unit per liter (U/L)	Standard Deviation 9.08
Treatment B	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	16.9 Unit per liter (U/L)	Standard Deviation 10
Treatment B	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	71.1 Unit per liter (U/L)	Standard Deviation 13.2
Treatment B	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	69.9 Unit per liter (U/L)	Standard Deviation 14.06
Treatment B	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	63.6 Unit per liter (U/L)	Standard Deviation 18.27
Treatment B	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	65.2 Unit per liter (U/L)	Standard Deviation 15.66
Treatment B	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	20.1 Unit per liter (U/L)	Standard Deviation 4.43
Treatment B	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	17.8 Unit per liter (U/L)	Standard Deviation 3.81
Treatment B	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	21.1 Unit per liter (U/L)	Standard Deviation 5.66
Treatment B	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	14.1 Unit per liter (U/L)	Standard Deviation 5.49

Secondary

AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

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).

Population: PK Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment B	AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide; n= 37, 38	2490 h*ng/mL	Geometric Coefficient of Variation 18.3
Treatment B	AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride; n= 22, 22	112 h*ng/mL	Geometric Coefficient of Variation 18.2

90% CI: [88.75, 96.12]

90% CI: [97.84, 105.23]

Secondary

Blood Urea Nitrogen (BUN) Levels at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment B	Blood Urea Nitrogen (BUN) Levels at Indicated Time Points	P2; Day 3; 48 hour post-dose; n=19, 19	15.208 Milligrams per deciliter (mg/dL)	Standard Deviation 3.493
Treatment B	Blood Urea Nitrogen (BUN) Levels at Indicated Time Points	P1; Day-1; 24 hour pre-dose; n=21, 21	12.702 Milligrams per deciliter (mg/dL)	Standard Deviation 3.954
Treatment B	Blood Urea Nitrogen (BUN) Levels at Indicated Time Points	P2; Day -1; 24 hour pre-dose; n=19, 19	12.164 Milligrams per deciliter (mg/dL)	Standard Deviation 3.216
Treatment B	Blood Urea Nitrogen (BUN) Levels at Indicated Time Points	P1; Day 3; 48 hour post-dose; n=21, 20	15.593 Milligrams per deciliter (mg/dL)	Standard Deviation 3.02

Secondary

Body Temperature Values at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day1; 1 hour post-dose; n= 21, 21	36.44 Degree Celsius	Standard Deviation 0.262
Treatment A	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
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day1; 2 hour post-dose; n= 21, 21	36.42 Degree Celsius	Standard Deviation 0.339
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day1; 4 hour post-dose; n= 21, 21	36.45 Degree Celsius	Standard Deviation 0.364
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day1; 6 hour post-dose; n= 21, 21	36.59 Degree Celsius	Standard Deviation 0.422
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day1; 8 hour post-dose; n= 21, 21	36.64 Degree Celsius	Standard Deviation 0.461
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day2; 24 hour post-dose; n= 21, 21	36.28 Degree Celsius	Standard Deviation 0.387
Treatment A	Body Temperature Values at Indicated Time Points	P1; Day3; 48 hour post-dose; n= 21, 20	36.26 Degree Celsius	Standard Deviation 0.334
Treatment A	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
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day1; 1 hour post-dose; n= 19, 19	36.28 Degree Celsius	Standard Deviation 0.302
Treatment A	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
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day1; 2 hour post-dose; n= 19, 19	36.41 Degree Celsius	Standard Deviation 0.294
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day1; 4 hour post-dose; n= 19, 19	36.53 Degree Celsius	Standard Deviation 0.335
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day1; 6 hour post-dose; n= 19, 19	36.59 Degree Celsius	Standard Deviation 0.331
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day1; 8 hour post-dose; n= 19, 19	36.64 Degree Celsius	Standard Deviation 0.383
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day2; 24 hour post-dose; n= 19, 19	36.15 Degree Celsius	Standard Deviation 0.301
Treatment A	Body Temperature Values at Indicated Time Points	P2; Day3; 48 hour post-dose; n= 18, 19	36.08 Degree Celsius	Standard Deviation 0.323
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day1; 4 hour post-dose; n= 19, 19	36.44 Degree Celsius	Standard Deviation 0.38
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day-1; 12 hour pre-dose; n= 21, 21	36.43 Degree Celsius	Standard Deviation 0.376
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day-1; 12 hour pre-dose; n= 19, 19	36.34 Degree Celsius	Standard Deviation 0.383
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day1; 1 hour post-dose; n= 21, 21	36.40 Degree Celsius	Standard Deviation 0.392
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day3; 48 hour post-dose; n= 18, 19	36.28 Degree Celsius	Standard Deviation 0.486
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day1; 1.5 hour post-dose; n= 21, 21	36.05 Degree Celsius	Standard Deviation 0.314
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day1; 1 hour post-dose; n= 19, 19	36.24 Degree Celsius	Standard Deviation 0.435
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day1; 2 hour post-dose; n= 21, 21	36.38 Degree Celsius	Standard Deviation 0.314
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day1; 6 hour post-dose; n= 19, 19	36.57 Degree Celsius	Standard Deviation 0.406
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day1; 4 hour post-dose; n= 21, 21	36.46 Degree Celsius	Standard Deviation 0.365
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day1; 1.5 hour post-dose; n= 19, 19	36.19 Degree Celsius	Standard Deviation 0.336
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day1; 6 hour post-dose; n= 21, 21	36.61 Degree Celsius	Standard Deviation 0.309
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day2; 24 hour post-dose; n= 19, 19	36.17 Degree Celsius	Standard Deviation 0.437
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day1; 8 hour post-dose; n= 21, 21	36.75 Degree Celsius	Standard Deviation 0.357
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day1; 2 hour post-dose; n= 19, 19	36.38 Degree Celsius	Standard Deviation 0.405
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day2; 24 hour post-dose; n= 21, 21	36.30 Degree Celsius	Standard Deviation 0.322
Treatment B	Body Temperature Values at Indicated Time Points	P2; Day1; 8 hour post-dose; n= 19, 19	36.65 Degree Celsius	Standard Deviation 0.399
Treatment B	Body Temperature Values at Indicated Time Points	P1; Day3; 48 hour post-dose; n= 21, 20	36.28 Degree Celsius	Standard Deviation 0.374

Secondary

Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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 1.48
Treatment A	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 1.41
Treatment A	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
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Sodium; P2; Day-1; 24 hour pre-dose; n= 19, 19	139.68 Millimoles per liter (Mmol/L)	Standard Deviation 2.187
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Magnesium; P1; Day-1; 24 hour pre-dose; n= 21, 21	0.801 Millimoles per liter (Mmol/L)	Standard Deviation 0.049
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Calcium; P1; Day-1; 24 hour pre-dose; n= 21, 21	2.418 Millimoles per liter (Mmol/L)	Standard Deviation 0.085
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Potassium; P2; Day-1; 24 hour pre-dose; n= 19, 19	4.225 Millimoles per liter (Mmol/L)	Standard Deviation 0.289
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Calcium; P1; Day 3; 48 hour post-dose; n= 21, 20	2.393 Millimoles per liter (Mmol/L)	Standard Deviation 0.071
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Magnesium; P1; Day 3; 48 hour post-dose; n= 21, 20	0.804 Millimoles per liter (Mmol/L)	Standard Deviation 0.044
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Calcium; P2; Day-1; 24 hour pre-dose; n= 19, 19	2.335 Millimoles per liter (Mmol/L)	Standard Deviation 0.074
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Sodium; P1; Day 3; 48 hour post-dose; n= 21, 20	139.25 Millimoles per liter (Mmol/L)	Standard Deviation 1.41
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Calcium; P2; Day 3; 48 hour post-dose; n= 19, 19	2.379 Millimoles per liter (Mmol/L)	Standard Deviation 0.069
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Chloride; P1; Day-1; 24 hour pre-dose; n= 21, 21	103.62 Millimoles per liter (Mmol/L)	Standard Deviation 2.225
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Magnesium; P2; Day-1; 24 hour pre-dose; n= 19, 19	0.805 Millimoles per liter (Mmol/L)	Standard Deviation 0.053
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Chloride; P1; Day 3; 48 hour post-dose; n= 21, 20	102.63 Millimoles per liter (Mmol/L)	Standard Deviation 2.011
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Potassium; P2; Day 3; 48 hour post-dose; n= 19, 19	4.336 Millimoles per liter (Mmol/L)	Standard Deviation 0.288
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Chloride; P2; Day-1; 24 hour pre-dose; n= 19, 19	104.85 Millimoles per liter (Mmol/L)	Standard Deviation 2.252
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Magnesium; P2; Day 3; 48 hour post-dose; n= 19, 19	0.783 Millimoles per liter (Mmol/L)	Standard Deviation 0.052
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Chloride; P2; Day 3; 48 hour post-dose; n= 19, 19	103.49 Millimoles per liter (Mmol/L)	Standard Deviation 1.882
Treatment B	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 2.424
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Glucose; P1; Day-1; 24 hour pre-dose; n= 21, 20	4.643 Millimoles per liter (Mmol/L)	Standard Deviation 0.427
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Potassium; P1; Day-1; 24 hour pre-dose; n= 21, 21	4.294 Millimoles per liter (Mmol/L)	Standard Deviation 0.39
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Glucose; P1; Day 3; 48 hour post-dose; n= 21, 20	4.827 Millimoles per liter (Mmol/L)	Standard Deviation 0.368
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Sodium; P1; Day-1; 24 hour pre-dose; n= 21, 21	140.67 Millimoles per liter (Mmol/L)	Standard Deviation 1.958
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Glucose; P2; Day-1; 24 hour pre-dose; n= 19, 19	4.765 Millimoles per liter (Mmol/L)	Standard Deviation 0.354
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Potassium; P1; Day 3; 48 hour post-dose; n= 21, 20	4.222 Millimoles per liter (Mmol/L)	Standard Deviation 0.438
Treatment B	Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points	Glucose; P2; Day 3; 48 hour post-dose; n= 19, 19	4.732 Millimoles per liter (Mmol/L)	Standard Deviation 0.282

Secondary

Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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 5.92
Treatment A	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
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Total bilirubin;P2;Day3;48 hour post-dose;n=19,19	8.67 Micromoles per liter (µmol/L)	Standard Deviation 4.492
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Creatinine; P1; Day-1; 24 hour pre-dose; n= 21, 21	85.0 Micromoles per liter (µmol/L)	Standard Deviation 11.51
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Creatinine; P1; Day3; 48 hour post-dose; n= 21, 20	87.3 Micromoles per liter (µmol/L)	Standard Deviation 12.18
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Creatinine; P2; Day-1; 24 hour pre-dose; n= 19, 19	82.5 Micromoles per liter (µmol/L)	Standard Deviation 13.33
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Creatinine; P2; Day3; 48 hour post-dose; n= 19, 19	88.7 Micromoles per liter (µmol/L)	Standard Deviation 16.69
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Direct bilirubin;P1;Day-1;24 hour pre-dose;n=21,21	4.52 Micromoles per liter (µmol/L)	Standard Deviation 1.825
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Direct bilirubin;P1;Day3;48 hour post-dose;n=21,20	3.72 Micromoles per liter (µmol/L)	Standard Deviation 1.493
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Direct bilirubin;P2;Day-1;24 hour pre-dose;n=19,19	3.64 Micromoles per liter (µmol/L)	Standard Deviation 1.446
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Direct bilirubin;P2;Day3;48 hour post-dose;n=19,19	3.14 Micromoles per liter (µmol/L)	Standard Deviation 1.34
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Total bilirubin;P1;Day-1;24 hour pre-dose;n=21,21	13.48 Micromoles per liter (µmol/L)	Standard Deviation 6.923
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Total bilirubin;P1;Day3;48 hour post-dose;n=21,20	10.80 Micromoles per liter (µmol/L)	Standard Deviation 5.601
Treatment B	Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points	Total bilirubin;P2;Day-1;24 hour pre-dose;n=19,19	10.08 Micromoles per liter (µmol/L)	Standard Deviation 5.119

Secondary

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period

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

Time frame: Up to 25 days

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

Arm	Measure	Group	Value (NUMBER)
Treatment A	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period	AEs	5 Participants
Treatment A	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period	SAEs	0 Participants
Treatment B	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period	AEs	8 Participants
Treatment B	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period	SAEs	0 Participants

Secondary

Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

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).

Population: PK Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment B	Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide; n= 37, 38	4.63 Percent of area	Geometric Coefficient of Variation 33.2
Treatment B	Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride; n= 22, 22	10.7 Percent of area	Geometric Coefficient of Variation 44.9

Secondary

Pulse Rate Values at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day1; 4 hour post-dose; n= 19, 19	62.7 Beats per minute (bpm)	Standard Deviation 11.36
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day-1; 12 hour pre-dose; n= 21, 21	64.7 Beats per minute (bpm)	Standard Deviation 9.57
Treatment B	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 11.95
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day1; 1 hour post-dose; n= 21, 21	62.0 Beats per minute (bpm)	Standard Deviation 10.26
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day3; 48 hour post-dose; n= 18, 19	73.4 Beats per minute (bpm)	Standard Deviation 17.13
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day1; 1.5 hour post-dose; n= 21, 21	60.9 Beats per minute (bpm)	Standard Deviation 11.05
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day1; 1 hour post-dose; n= 19, 19	60.1 Beats per minute (bpm)	Standard Deviation 9.72
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day1; 2 hour post-dose; n= 21, 21	60.7 Beats per minute (bpm)	Standard Deviation 8.97
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day1; 6 hour post-dose; n= 19, 19	71.4 Beats per minute (bpm)	Standard Deviation 13.25
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day1; 4 hour post-dose; n= 21, 21	62.5 Beats per minute (bpm)	Standard Deviation 9.91
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day1; 1.5 hour post-dose; n= 19, 19	62.8 Beats per minute (bpm)	Standard Deviation 10.97
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day1; 6 hour post-dose; n= 21, 21	70.8 Beats per minute (bpm)	Standard Deviation 10.17
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day2; 24 hour post-dose; n= 19, 19	68.8 Beats per minute (bpm)	Standard Deviation 13.29
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day1; 8 hour post-dose; n= 21, 21	67.8 Beats per minute (bpm)	Standard Deviation 9.33
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day1; 2 hour post-dose; n= 19, 19	59.2 Beats per minute (bpm)	Standard Deviation 8.6
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day2; 24 hour post-dose; n= 21, 21	68.6 Beats per minute (bpm)	Standard Deviation 10.18
Treatment B	Pulse Rate Values at Indicated Time Points	P2; Day1; 8 hour post-dose; n= 19, 19	66.2 Beats per minute (bpm)	Standard Deviation 11.26
Treatment B	Pulse Rate Values at Indicated Time Points	P1; Day3; 48 hour post-dose; n= 21, 20	73.0 Beats per minute (bpm)	Standard Deviation 9.49

Secondary

Respiratory Rate Values at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	Respiratory Rate Values at Indicated Time Points	P1; Day1; 1 hour post-dose; n= 21, 21	16.3 Breaths per minute	Standard Deviation 2.7
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day1; 4 hour post-dose; n= 19, 19	17.4 Breaths per minute	Standard Deviation 2.5
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day-1; 12 hour pre-dose; n= 21, 21	17.0 Breaths per minute	Standard Deviation 1.45
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day-1; 12 hour pre-dose; n= 19, 19	17.2 Breaths per minute	Standard Deviation 1.54
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day1; 1 hour post-dose; n= 21, 21	17.0 Breaths per minute	Standard Deviation 2.33
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day3; 48 hour post-dose; n= 18, 19	17.2 Breaths per minute	Standard Deviation 2.42
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day1; 1.5 hour post-dose; n= 21, 21	17.9 Breaths per minute	Standard Deviation 1.62
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day1; 1 hour post-dose; n= 19, 19	17.9 Breaths per minute	Standard Deviation 1.56
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day1; 2 hour post-dose; n= 21, 21	17.5 Breaths per minute	Standard Deviation 2.36
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day1; 6 hour post-dose; n= 19, 19	18.3 Breaths per minute	Standard Deviation 2.52
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day1; 4 hour post-dose; n= 21, 21	17.0 Breaths per minute	Standard Deviation 2.25
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day1; 1.5 hour post-dose; n= 19, 19	16.3 Breaths per minute	Standard Deviation 1.82
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day1; 6 hour post-dose; n= 21, 21	18.4 Breaths per minute	Standard Deviation 2.16
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day2; 24 hour post-dose; n= 19, 19	17.6 Breaths per minute	Standard Deviation 1.64
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day1; 8 hour post-dose; n= 21, 21	18.2 Breaths per minute	Standard Deviation 1.89
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day1; 2 hour post-dose; n= 19, 19	17.3 Breaths per minute	Standard Deviation 2.84
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day2; 24 hour post-dose; n= 21, 21	18.0 Breaths per minute	Standard Deviation 1.8
Treatment B	Respiratory Rate Values at Indicated Time Points	P2; Day1; 8 hour post-dose; n= 19, 19	18.2 Breaths per minute	Standard Deviation 2.1
Treatment B	Respiratory Rate Values at Indicated Time Points	P1; Day3; 48 hour post-dose; n= 21, 20	17.7 Breaths per minute	Standard Deviation 1.89

Secondary

Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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 8.9
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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 7.1
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP: P2; Day2; 24 hour post-dose; n= 19, 19	110.6 Millimeters of mercury (mmHg)	Standard Deviation 10.03
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP: P1; Day3; 48 hour post-dose; n= 21, 20	66.0 Millimeters of mercury (mmHg)	Standard Deviation 6.38
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P2; Day3; 48 hour post-dose; n= 18, 19	116.5 Millimeters of mercury (mmHg)	Standard Deviation 9.18
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP: P2; Day3; 48 hour post-dose; n= 18, 19	67.2 Millimeters of mercury (mmHg)	Standard Deviation 6.64
Treatment B	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	64.9 Millimeters of mercury (mmHg)	Standard Deviation 7.25
Treatment B	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	115.8 Millimeters of mercury (mmHg)	Standard Deviation 8.99
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP: P2; Day2; 24 hour post-dose; n= 19, 19	64.4 Millimeters of mercury (mmHg)	Standard Deviation 7.79
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P1; Day1; 1 hour post-dose; n= 21, 21	111.6 Millimeters of mercury (mmHg)	Standard Deviation 7.56
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P1; Day1; 1 hour post-dose; n= 21, 21	63.5 Millimeters of mercury (mmHg)	Standard Deviation 5.55
Treatment B	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	110.8 Millimeters of mercury (mmHg)	Standard Deviation 11.01
Treatment B	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	65.8 Millimeters of mercury (mmHg)	Standard Deviation 7.65
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P1; Day1; 2 hour post-dose; n= 21, 21	112.6 Millimeters of mercury (mmHg)	Standard Deviation 7.95
Treatment B	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	63.9 Millimeters of mercury (mmHg)	Standard Deviation 8.57
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP: P1; Day1; 4 hour post-dose; n= 21, 21	114.0 Millimeters of mercury (mmHg)	Standard Deviation 9.3
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P2; Day1; 4 hour post-dose; n= 19, 19	65.3 Millimeters of mercury (mmHg)	Standard Deviation 8.08
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P1; Day1; 6 hour post-dose; n= 21, 21	113.0 Millimeters of mercury (mmHg)	Standard Deviation 8.26
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P1; Day1; 2 hour post-dose; n= 21, 21	65.7 Millimeters of mercury (mmHg)	Standard Deviation 9.45
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P1; Day1; 8 hour post-dose; n= 21, 21	111.8 Millimeters of mercury (mmHg)	Standard Deviation 8.62
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P2; Day1; 1 hour post-dose; n= 19, 19	64.1 Millimeters of mercury (mmHg)	Standard Deviation 8.39
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P1; Day2; 24 hour post-dose; n= 21, 21	110.5 Millimeters of mercury (mmHg)	Standard Deviation 6.79
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP: P1; Day1; 4 hour post-dose; n= 21, 21	64.4 Millimeters of mercury (mmHg)	Standard Deviation 7.21
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P1; Day3; 48 hour post-dose; n= 21, 20	113.8 Millimeters of mercury (mmHg)	Standard Deviation 9.2
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P2; Day1; 8 hour post-dose; n= 19, 19	62.9 Millimeters of mercury (mmHg)	Standard Deviation 6.75
Treatment B	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	116.2 Millimeters of mercury (mmHg)	Standard Deviation 10.04
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P1; Day1; 6 hour post-dose; n= 21, 21	62.7 Millimeters of mercury (mmHg)	Standard Deviation 6.2
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P2; Day1; 1 hour post-dose; n= 19, 19	113.7 Millimeters of mercury (mmHg)	Standard Deviation 11.71
Treatment B	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	112.2 Millimeters of mercury (mmHg)	Standard Deviation 12.62
Treatment B	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	63.4 Millimeters of mercury (mmHg)	Standard Deviation 8.64
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP; P2; Day1; 2 hour post-dose; n= 19, 19	113.8 Millimeters of mercury (mmHg)	Standard Deviation 12.49
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P1; Day1; 8 hour post-dose; n= 21, 21	63.7 Millimeters of mercury (mmHg)	Standard Deviation 6.02
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP: P2; Day1; 4 hour post-dose; n= 19, 19	113.5 Millimeters of mercury (mmHg)	Standard Deviation 11.57
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP: P2; Day1; 6 hour post-dose; n= 19, 19	61.5 Millimeters of mercury (mmHg)	Standard Deviation 6.33
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP: P2; Day1; 6 hour post-dose; n= 19, 19	112.4 Millimeters of mercury (mmHg)	Standard Deviation 10.79
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP: P1; Day2; 24 hour post-dose; n= 21, 21	64.2 Millimeters of mercury (mmHg)	Standard Deviation 5.86
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	SBP: P2; Day1; 8 hour post-dose; n= 19, 19	111.5 Millimeters of mercury (mmHg)	Standard Deviation 12.04
Treatment B	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points	DBP; P2; Day1; 2 hour post-dose; n= 19, 19	65.3 Millimeters of mercury (mmHg)	Standard Deviation 7.28

Secondary

Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

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).

Population: PK Population

Arm	Measure	Group	Value (MEDIAN)
Treatment A	Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide; n= 37, 38	12.4 Hour
Treatment A	Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride; n= 22, 22	15.2 Hour
Treatment B	Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide; n= 37, 38	11.3 Hour
Treatment B	Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride; n= 22, 22	16.6 Hour

Secondary

Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

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.

Population: PK Population

Arm	Measure	Group	Value (MEDIAN)
Treatment A	Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide	2.505 Hour
Treatment A	Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride	2.507 Hour
Treatment B	Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Hydrochlorothiazide	1.509 Hour
Treatment B	Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma	Amiloride	2.508 Hour

Secondary

Total Protein Levels at Indicated Time Points

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).

Time frame: Day -1 and Day 3 of each treatment period

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A	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
Treatment A	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
Treatment A	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
Treatment A	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
Treatment B	Total Protein Levels at Indicated Time Points	P2; Day 3; 48 hours post-dose; n= 19, 19	72.33 Grams per liter (g/L)	Standard Deviation 4.241
Treatment B	Total Protein Levels at Indicated Time Points	P1; Day-1; 24 hours pre-dose; n= 21, 21	76.06 Grams per liter (g/L)	Standard Deviation 3.733
Treatment B	Total Protein Levels at Indicated Time Points	P2; Day-1; 24 hours pre-dose; n= 19, 19	70.06 Grams per liter (g/L)	Standard Deviation 4.002
Treatment B	Total Protein Levels at Indicated Time Points	P1; Day 3; 48 hours post-dose; n= 21, 20	74.99 Grams per liter (g/L)	Standard Deviation 3.844

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

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Outcome results

Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride

Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points

AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

Blood Urea Nitrogen (BUN) Levels at Indicated Time Points

Body Temperature Values at Indicated Time Points

Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points

Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period

Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

Pulse Rate Values at Indicated Time Points

Respiratory Rate Values at Indicated Time Points

Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points

Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma

Total Protein Levels at Indicated Time Points