Pivotal Bioequivalence Study to Qualify Manufacturing Site Transfer for Prazosin Hydrochloride Capsules

A 2 COHORT, SINGLE DOSE, OPEN-LABEL, RANDOMIZED, PIVOTAL BIOEQUIVALENCE STUDY TO QUALIFY MANUFACTURING SITE TRANSFER FROM BARCELONETA TO ASCOLI FOR PRAZOSIN HYDROCHLORIDE CAPSULES IN HEALTHY ADULT PARTICIPANTS UNDER FASTED CONDITIONS

Prazosin hydrochloride (HCl) is an oral anti-hypertensive indicated for the treatment of primary and secondary hypertension and heart failure. Pfizer Inc. is the marketing authorization holder for prazosin HCl oral capsules and intended to transfer drug product manufacturing operations from Pfizer, Barceloneta Puerto Rico to Pfizer Pharmaceutical, Ascoli, Italy. To support the manufacturer site transfer and process changes, this bioequivalence (BE) study is being conducted.

This study will be a 2 Cohort, open-label, randomized, single dose study in healthy adult male and/or female participants. Cohort 1 will be crossover with 3 treatments, 3 periods, 6 sequences. Cohort 2 will be crossover with 2 treatments, 2 periods, 2 sequences. Primary objective of this study is demonstrate bioequivalence between prazosin HCl 1, 2 and 5 mg capsules manufactured at Ascoli versus prazosin HCl 2 and 5 mg capsules manufactured at Barceloneta under fasting conditions in healthy adult participants. Approximately 36 participants will be enrolled in each Cohort 1 and Cohort 2.

Pharmacokinetic and statistical analysis will be performed for prazosin. Data from 2 Cohorts will be analyzed separately. The PK parameters area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast), and from time zero extrapolated to infinite time (AUCinf), maximum plasma concentration (Cmax), time to first occurrence of Cmax (Tmax), and terminal phase elimination half-life (t½) will be summarized descriptively by analyte and treatment.

For primary objective, bioequivalence of the Test treatment relative to Reference treatment will be concluded if the 90% confidence intervals (CI) for the ratio of adjusted geometric means of Test treatments relative to Reference treatment for AUCinf (if data permit), AUClast and Cmax, fall wholly within (80%, 125%).

Study Overview

• Status: Completed
• Conditions: Heart Failure; Hypertension
• Intervention / Treatment: Drug: Prazosin HCl 2mg; Drug: Prazosin HCl 1 mg; Drug: Prazosin HCl 5 mg

• Study Type: Interventional
• Enrollment (Actual): 72
• 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: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants must be 18 to 55 years of age, inclusive, at the time of signing the Informed Consent Document (ICD).
• Male and female participants who are overtly healthy as determined by medical evaluation including medical history, full physical examination, vital signs, 12-lead electrocardiogram (ECG), and/or clinical laboratory tests.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations , and other study procedures.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• History of Human Immunodeficiency Virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
• 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.
• A positive urine drug test.
• Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
• Baseline standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
• Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:
• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.5 × upper limit of normal (ULN);
• Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
• Use of tobacco or nicotine containing products in excess of the equivalent of 5 cigarettes per day. For chewing tobacco, one chew is equivalent to approximately 2 to 3 cigarettes, so participants would be limited to 2 or less chews per day.
• History of sensitivity to prazosin hydrochloride or any of the components in the formulation of the study products.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prazosin Hydrochloride (HCL) 2 milligram (mg) capsule Barceloneta site; One 2 mg capsule manufactured at the current site, Barceloneta	Drug: Prazosin HCl 2mg; Prazosin HCL 1 X 2 mg capsule.; Other Names: Minipress 2 mg capsule.
Experimental: Prazosin HCL 2 mg capsule Ascoli site; One 2 mg capsule manufactured at the proposed site (Ascoli)	Drug: Prazosin HCl 2mg; Prazosin HCL 1 X 2 mg capsule.; Other Names: Minipress 2 mg capsule.
Experimental: Prazosin HCL 1 mg capsule Ascoli site; Two 1 mg capsule manufactured at the proposed site, Ascoli	Drug: Prazosin HCl 1 mg; Prazosin HCl 2 X 1 mg capsule.; Other Names: Minipress 1 mg capsule.
Active Comparator: Prazosin HCL 5 mg capsule Barceloneta site; One 5 mg capsule manufactured at the current site, Barceloneta	Drug: Prazosin HCl 5 mg; Prazosin HCL 1 X 5 mg capsule.; Other Names: Minipress 5 mg capsule.
Active Comparator: Prazosin HCL 1 x 5 mg capsule Ascoli site; One 5 mg capsule manufactured at the proposed site, Ascoli	Drug: Prazosin HCl 5 mg; Prazosin HCL 1 X 5 mg capsule.; Other Names: Minipress 5 mg capsule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Prazosin	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of each period
Maximum Observed Plasma Concentration (Cmax) of Prazosin	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Prazosin		0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of each period
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Prazosin		0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of each period
Plasma Decay Half-Life (t1/2) of Prazosin	Plasma terminal elimination half-life of Prazosin was measured.	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of each period
Number of Participants With Adverse Events (AEs) According to Seriousness	Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). Time frame for safety monitoring was from screening to Follow-Up Completion (Day 35 after the last dose administration of the last period), and the actual time frame might vary according to the number of doses received and the length of washing period of each dose for each participant.	Time frame varied from 20 days to 94 days for cohort 1, and 8 days to 73 days for cohort 2.

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): September 22, 2021
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): February 15, 2022

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Prazosin
• Other Study ID Numbers: A0281006

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