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

NCT04967443 | Completed Phase 1 Results FDA Drug

• 1 other identifier: A0281006
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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%).

Conditions

Hypertension; Heart Failure

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

  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

  Time frame varied from 20 days to 94 days for cohort 1, and 8 days to 73 days for cohort 2.

Study Arms (5)

Prazosin Hydrochloride (HCL) 2 milligram (mg) capsule Barceloneta site

ACTIVE COMPARATOR

One 2 mg capsule manufactured at the current site, Barceloneta

Drug: Prazosin HCl 2mg

Prazosin HCL 2 mg capsule Ascoli site

EXPERIMENTAL

One 2 mg capsule manufactured at the proposed site (Ascoli)

Drug: Prazosin HCl 2mg

Prazosin HCL 1 mg capsule Ascoli site

EXPERIMENTAL

Two 1 mg capsule manufactured at the proposed site, Ascoli

Drug: Prazosin HCl 1 mg

Prazosin HCL 5 mg capsule Barceloneta site

ACTIVE COMPARATOR

One 5 mg capsule manufactured at the current site, Barceloneta

Drug: Prazosin HCl 5 mg

Prazosin HCL 1 x 5 mg capsule Ascoli site

ACTIVE COMPARATOR

One 5 mg capsule manufactured at the proposed site, Ascoli

Drug: Prazosin HCl 5 mg

Interventions

Prazosin HCl 2mg DRUG

Prazosin HCL 1 X 2 mg capsule.

Also known as: Minipress 2 mg capsule.

Prazosin HCL 2 mg capsule Ascoli site; Prazosin Hydrochloride (HCL) 2 milligram (mg) capsule Barceloneta site

Prazosin HCl 1 mg DRUG

Prazosin HCl 2 X 1 mg capsule.

Also known as: Minipress 1 mg capsule.

Prazosin HCL 1 mg capsule Ascoli site

Prazosin HCl 5 mg DRUG

Prazosin HCL 1 X 5 mg capsule.

Also known as: Minipress 5 mg capsule.

Prazosin HCL 1 x 5 mg capsule Ascoli site; Prazosin HCL 5 mg capsule Barceloneta site

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Clinical Trials of Texas, LLC

San Antonio, Texas, 78229, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Hypertension; Heart Failure

Interventions

Prazosin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: September 22, 2021
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2022
• Last Updated: July 12, 2024
• Results First Posted: July 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)