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

Phase 1

Completed

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

• Registration Number: NCT06205407
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-26
• Study First Submitted: 2024-01-02
• Study First Submitted QC: 2024-01-11
• Study First Posted: 2024-01-16
• Primary Completion: 2024-03-01
• Study Completion: 2024-03-01
• Status Verified: 2025-02
• Results First Submitted: 2025-02-28
• Results First Submitted QC: 2025-02-28
• Last Update Submitted: 2025-02-28
• Results First Posted: 2025-03-21
• Last Update Posted: 2025-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A	Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Viatris	Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets manufactured at Viatris.
Treatment B	Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Neolpharma.	Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets manufactured at Neolpharma.

Primary Outcome Measures

Name	Time	Method
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	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	Maximum plasma concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Viatris.
Cmax of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet 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	Maximum plasma concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Neolpharma.
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	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 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.
AUCinf of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet 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	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.

Secondary Outcome Measures

Name	Time	Method
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	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 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.
t1/2 of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet 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	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 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	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 maximum concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Viatris.
Tmax of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet 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 maximum concentration of Spironolactone and Hydrochlorothiazide after participants received a single oral dose of 25/25 mg film coated tablets manufactured at Neolpharma.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)	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.
Number of Participants With Laboratory Test Abnormalities Meeting AE Criteria (Without Regard to Baseline Abnormality)	From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)	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.
Number of Participants With Vital Signs Data Meeting AE Criteria	From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)	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.
Number of Participants With Electrocardiogram (ECG) Data Meeting AE Criteria	From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)	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.

Trial Locations

Locations (1)

Clinical Trials of Texas, LLC; 🇺🇸 San Antonio, Texas, United States