A Study to Learn How the Body Processes Spironolactone and Hydrochlorothiazide Film Coated Tablets Manufactured at Two Sites: Viatris and Neolpharma

A Single-dose, Open-label, Randomized, 2-way, Cross-over Pivotal Bioequivalence Study to Qualify Manufacturing Site Transfer From Viatris to Neolpharma, for Spironolactone/Hydrochlorothiazide Film Coated Tablets in Healthy Adult Participants Under Fasted Conditions.

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 Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Viatris; Drug: Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Neolpharma.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female participants must be 18 to 75 years of age, inclusive, at the time of signing the ICD.
2. BMI of 16-32 kg/m2; and a total body weight >50 kg (110 lb).
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

   1. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
   2. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
2. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
3. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
4. Current use of any prohibited concomitant medication(s) or participant unwilling or unable to use a required concomitant medication(s).
5. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
6. A positive urine drug test. A single repeat for positive drug screen may be allowed.
7. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If systolic BP is ≥ 140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.

8. Hepatic dysfunction defined as:

   1. Total bilirubin ≥1.5 × ULN (For Gilbert's syndrome, direct bilirubin >ULN is exclusionary)
   2. AST ≥1.5 × ULN
   3. ALT ≥1.5 × ULN
9. Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms). If QTcF exceeds 450 ms, the ECG should be repeated twice and the average of the 3 QTcF values used to determine the participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
10. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
12. History of sensitivity to heparin or heparin induced thrombocytopenia.
13. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
14. History of hypersensitivity to spironolactone or HCTZ or any of the components in the formulation of the study products, or allergic to thiazide diuretics or to other sulfonamide-derived drugs.
15. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets manufactured at Viatris.	Drug: Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Viatris; Manufactured at Viatris
Experimental: Treatment B; Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets manufactured at Neolpharma.	Drug: Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Neolpharma.; Manufactured at Neolpharma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2023
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bioequivalence; Phase I; Spironolactone/Hydrochlorothiazide film coated tablets
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Hormone Antagonists; Diuretics; Natriuretic Agents; Antihypertensive Agents; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Sodium Chloride Symporter Inhibitors; Spironolactone; Hydrochlorothiazide
• Other Study ID Numbers: B9531002; NCT06205407 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No