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

Study Overview
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Brief Summary
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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%).

Official Title
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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

Conditions
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Hypertension, Heart Failure

Intervention / Treatment
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* Drug: Prazosin HCl 2mg
* Drug: Prazosin HCl 1 mg
* Drug: Prazosin HCl 5 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |  | 24 hours | 
| Maximum Observed Plasma Concentration (Cmax) of Prazosin |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) |  | 24 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Prazosin |  | 24 hours | 
| Plasma Decay Half-Life (t 1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 24 hours | 
| Number of Participants With Adverse Events (AEs) According to Seriousness |  | Baseline, up to 28 days post last dose. |