Clinical trial NCT06205407: A Study to Learn How the Body Processes Spironolactone and Hydrochlorothiazide Film Coated Tablets Manufactured at Two Sites: Viatris and Neolpharma
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Phase I
Pharmacokinetics
Spironolactone/Hydrochlorothiazide film coated tablets
Bioequivalence
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-01-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be an open-label, randomized, single-dose, 2-treatment, 2-period, 2-sequence, crossover study in adult healthy male and/or female participants. Approximately 40 participants will be enrolled in the study (20 in each treatment sequence).

There will be a minimum 4-day washout period between successive doses (ie, administration of subsequent doses of study medication will not occur until at least 4 days after the previous dose of study medication).
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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
measure: Cmax of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
timeFrame: 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
measure: 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
timeFrame: 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
measure: AUCinf of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
timeFrame: 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 outcomes:
measure: 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
timeFrame: 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
measure: t1/2 of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
timeFrame: 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
measure: 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
timeFrame: 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
measure: Tmax of Spironolactone and Hydrochlorothiazide Following a Single Oral Dose of Spironolactone/Hydrochlorothiazide 25/25 mg Film Coated Tablet Manufactured at Neolpharma
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
measure: Number of Participants With Laboratory Test Abnormalities Meeting AE Criteria (Without Regard to Baseline Abnormality)
timeFrame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
measure: Number of Participants With Vital Signs Data Meeting AE Criteria
timeFrame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting AE Criteria
timeFrame: From Baseline up to 35 days after the last dose of study intervention (approximately 41 days)
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: