The purpose of the study is to understand how the body processes Spironolactone and Hydrochlorothiazide after taking Spironolactone and Hydrochlorothiazide film coated tablets manufactured at two sites: Viatris and Neolpharma by mouth. The study is seeking for: * Both male and female participants. * participants who must be 18 to 75 years of age. * Body Mass Index of participants should be 16 to 32 kilogram per meter squared and body weight should be more than 50 kilograms (110 pounds). About 40 participants will enter the study (20 in each group). Study consists of two periods. On Day 1 of each period, participants will receive a single amount of Spironolactone and Hydrochlorothiazide tablets. The total duration of study will be 71 days. Follow up may occur via telephone after 35 days after taking the final tablet of the study medicine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
42
Manufactured at Viatris
Manufactured at Neolpharma.
Clinical Trials of Texas, LLC
San Antonio, Texas, United States
Maximum Plasma Concentration (Cmax) of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Viatris
Maximum plasma concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Viatris.
Time frame: Pre-dose (0 hours [hrs]) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
Cmax of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
Maximum plasma concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Neolpharma.
Time frame: Pre-dose (0 hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Viatris
AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Area under the plasma concentration-time curve from time zero to infinity of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Viatris.
Time frame: Pre-dose (0 hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
AUCinf of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Area under the plasma concentration-time curve from time zero to infinity of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Neolpharma.
Time frame: Pre-dose (0 hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
Plasma Elimination Half Life (t1/2) of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Viatris
t1/2 was defined as terminal elimination half-life. Plasma elimination half life of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Viatris.
Time frame: Pre-dose (hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
t1/2 of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
t1/2 was defined as terminal elimination half-life. Plasma elimination half-life of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Neolpharma.
Time frame: Pre-dose (0 hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
Time to Reach Cmax (Tmax) of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Viatris
Time to reach maximum concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Viatris.
Time frame: Pre-dose (0 hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
Tmax of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
Time to reach maximum concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Neolpharma.
Time frame: Pre-dose (0 hrs) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any adverse events occurring following start of treatment were considered as treatment emergent adverse event (TEAE). Treatment-related TEAEs were determined by the investigator. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect.
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Time frame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
Number of Participants With Laboratory Test Abnormalities Meeting AE Criteria (Without Regard to Baseline Abnormality)
Abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) that met AE reporting criteria were those that worsened from baseline and considered clinically significant in the medical and scientific judgment of the investigator. Laboratory abnormalities that met any of the following conditions must be reported as an AE: (1) was associated with accompanying symptoms; (2) required additional diagnostic testing or medical/surgical intervention; (3) led to a change in study dosing (outside of any protocol-specified dose adjustments) or discontinuation from the study, significant additional concomitant drug treatment, or other therapy.
Time frame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
Number of Participants With Vital Signs Data Meeting AE Criteria
Abnormal vital sign measurement results (supine blood pressure, pulse rate) that met AE reporting criteria were those that worsened from baseline and considered clinically significant in the medical and scientific judgment of the investigator. Vital sign abnormalities that met any of the following conditions must be reported as an AE: (1) was associated with accompanying symptoms; (2) required additional diagnostic testing or medical/surgical intervention; (3) led to a change in study dosing (outside of any protocol-specified dose adjustments) or discontinuation from the study, significant additional concomitant drug treatment, or other therapy.
Time frame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
Number of Participants With Electrocardiogram (ECG) Data Meeting AE Criteria
Abnormal ECG results meeting AE reporting criteria were those that worsened from baseline, and considered clinically significant in the medical and scientific judgment of the investigator. ECG findings that may qualify as AE included: marked sinus bradycardia (rate \<40 beats per minute \[bpm\]) lasting minutes; new PR interval prolongation \>280 millisecond (ms); new prolongation of QT interval corrected using Fridericia's formula (QTcF) to \>480 ms (absolute); new prolongation of QTcF by \>60 ms from baseline; new onset atrial flutter or fibrillation, with controlled ventricular response rate: i.e., rate \<120 bpm; new onset type I second degree (Wenckebach) atrioventricular (AV) block of \>30-second duration; frequent premature ventricular contraction/complex (PVC), triplets, or short intervals (\<30 seconds) of consecutive ventricular complexes.
Time frame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)