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

Healthy Participants Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06205407
• Other study ID #: B9531002
• Status: Completed
• Phase: Phase 1
• Start date: December 26, 2023
• Est. completion date: March 1, 2024

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Viatris
Manufactured at Viatris
• Spironolactone/Hydrochlorothiazide (25 mg/25 mg) film coated tablets from Neolpharma.
Manufactured at Neolpharma.

Locations

Country	Name	City	State
United States	Clinical Trials of Texas, LLC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	Maximum observed plasma concentration (Cmax) of Spironolactone.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Primary	AUCinf (if data permit, otherwise AUClast)	Area Under the Curve from time zero to extrapolated infinite time (AUC0-inf) of Spironolactone.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Primary	Cmax	Maximum observed plasma concentration (Cmax) of Hydrochlorothiazide.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Primary	AUCinf (if data permit, otherwise AUClast)	Area Under the Curve from time zero to extrapolated infinite time (AUC0-inf) of Hydrochlorothiazide.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Secondary	AUClast	Area Under the Curve from time zero to last quantifiable concentration (AUClast) of Spironolactone and Hydrochlorothiazide.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Secondary	Tmax	Time to reach maximum observed plasma concentration (Tmax) of Spironolactone and Hydrochlorothiazide.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Secondary	t1/2	Plasma decay half-life (t1/2) of Spironolactone and Hydrochlorothiazide.	0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post dose
Secondary	Number of participants with Treatment Emergent Treatment-Related Adverse Events (AE's)		Baseline through Day 35
Secondary	Number of participants with clinically significant change from baseline in vital signs		Baseline through Day 35
Secondary	Number of participants with clinically significant change from baseline in Laboratory Abnormalities		During Screening

External Links

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