Study to Assess the Bioequivalence of Two Batches of Tamsulosin Hydrochloride in Healthy Male Subjects

A Single-dose, Randomized, Two-treatment, Two-period, Open-label, Crossover Study to Assess the Bioequivalence of Two Batches of Tamsulosin Hydrochloride 0.4-mg Capsules in Healthy Male Subjects

The objective of this study is to determine the bioequivalence of two batches of Flomax® 0.4 mg capsules in healthy male subjects. One is a commercial scale batch produced at the Nishine facility, and the other is a batch, of equal size, produced at the Norman II facility

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Flomax®, Norman II facility; Drug: Flomax®, Nishine facility

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Provide written informed consents, as evidenced by signature on an Informed Consent Form approved by the investigational review board (IRB) following a full explanation of the nature and purpose of the study
• Be a healthy male of any race between 18 and 40 years of age
• Have a body weight within 10 % of normal for sex, height, and frame as specified by the Body Weight Nomogram for Inclusion/Exclusion Criteria
• Have no clinically significant abnormalities o the basis of medical history, physical examination, and vital signs with no significant orthostatic blood pressure change, which is defined as no more than a 20 mm Hg drop in systolic blood pressure on assuming and maintaining the standing position for 3 minutes after being supine for at least 5 minutes. There should be no clinically significant symptoms associated with the orthostatic blood pressure testing procedure
• Have cardiovascular system that is within normal limits based on history, physical examination, and a 12-lead electrocardiogram (ECG)
• Have a negative test for ethanol by breathalyzer
• Have the ability to understand the requirements of the study, agree to abide by the study restrictions, and agree to return for the required assessments

Exclusion Criteria:

• Require ambulatory assistance (e.g., canes or walkers)
• Have a history of a "first dose hypotensive episode" upon starting therapy with an alpha-blocker
• Have a history of a pathological fall (unintentional change in body position) during the last year occurring under circumstances in which normal homeostatic mechanisms would ordinarily maintain stability or syncope
• Have any medical or laboratory abnormalities (liver function tests, blood urea nitrogen, and creatinine should not be outside the reference range for the clinical laboratory). Any subject who enters into the study with laboratory abnormalities must be approved by the Medical Monitor prior to enrollment
• Have abnormal alpha-1-acid glycoprotein values (i.e., values greater than 120 mg/dL)
• Have any history of acute angina attacks during the prior 6 months
• Have any abnormality of the ECG or a history of a documented myocardial infarction (electrocardiographic changes, serum enzymes increases, and hospitalization) during the prior 6 months, or evidence of any myocardial infarction on an ECG
• Have a New York Heart Association's Functional Classification of Heart Failure Class I, II, III, or IV
• Have a prior history of endocarditis
• Use any prescription medications within 2 weeks of dosing, or over-the-counter concomitant therapies with the exception of vitamins, dietary supplements, and acetaminophen within 7 days of dosing
• Have used an investigational drug within 1 month (30 days) of the Screening Period visit
• Donated blood within 1 month of entering study

• Have a known history of any of the following:

  • Clinically significant renal disease (renal dysfunction; i.e., creatinine greater than or equal to 2.0 mg/dL)
  • Severe cardiovascular disease (coarctation of the aorta, severe cardiac failure, second or third degree heart block, or severe angina)
  • Pulmonary disease (chronic lung disease or emphysema of a degree that could cause functional abnormalities of the right heart)
• Have acute illness (e.g., acute upper respiratory infection) within 2 weeks prior to the start of the study
• Have any medical condition that might interfere with either the absorption, distribution, metabolism, or excretion of tamsulosin
• Have a history of any illness or allergy that, in the opinion of the Investigator, might confound the results of the study or pose additional risk in administering Flomax® to the subject
• Have a history of liver disease or any physical findings suggestive of liver disease
• Have smoked within the last 3 months or be known as or be suspected as an alcohol abuser or illicit drug user within the past year, or have a positive urine drug screen
• Exhibit, in the opinion of the Investigator, the signs or symptoms of an immunodeficiency syndrome, whether spontaneously acquired, congenital, or iatrogenic (These syndromes are characterized by unusual susceptibility to infection [bacterial, viral, or fungal], the occurrence of autoimmune disease, and lymphoreticular malignancies)

• Have calculated creatinine clearance less than 90 mL/min based upon the following formula:

  • Creatinine Clearance = (140 - age in years) (weight in kg) / (72) (serum creatinine)
• Have a history of cancer except for nonmelanoma skin cancer treated by excision

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Flomax®, Nishine facility followed by Flomax®, Norman II facility	Drug: Flomax®, Norman II facility; Other Names: Tamsulosin hydrochloride; Drug: Flomax®, Nishine facility; Other Names: Tamsulosin hydrochloride
Experimental: Sequence 2; Flomax®, Norman II facility followed by Flomax®, Nishine facility	Drug: Flomax®, Norman II facility; Other Names: Tamsulosin hydrochloride; Drug: Flomax®, Nishine facility; Other Names: Tamsulosin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of the analyte in plasma at different time points (AUC)	Up to 48 h after drug administration
Maximum concentration of the analyte in plasma (Cmax)	Up to 48 h after drug administration
Time to reach the maximum concentration of the analyte in plasma (tmax)	Up to 48 h after drug administration
Elimination half-life (t1/2)	Up to 48 h after drug administration
Terminal elimination rate constant of the analyte in plasma (λz)	Up to 48 h after drug administration
Number of participants with clinically relevant changes in laboratory values	Up to day 3 after last drug administration
Number of participants with clinically relevant changes in vital signs (heart rate, orthostatic blood pressure, weight, temperature, respiration rate)	Up to day 3 after last drug administration
Number of participants with adverse events	Up to day 3 after last drug administration
Number of participants with clinically relevant changes in ECG	Up to day 3 after last drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 1999
• Primary Completion (Actual): September 1, 1999

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Estimate): October 17, 2014
• Last Update Submitted That Met QC Criteria: October 16, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin
• Other Study ID Numbers: 527.22