EC905 Pharmacokinetic Profile Study

An Open-label, Parallel Group, Randomized, Two-way Crossover, Multiple Dose Study to Compare the Pharmacokinetic Profiles of Solifenacin Succinate and Tamsulosin HCl Following Co-administration of Single Entity Tablets and Administration of Three Different Dose Strengths of the Combination Tablet EC905

A study to compare the pharmacokinetics of tamsulosin HCl and solifenacin succinate after co-administration of single entity tablets and of the combination tablet EC905 under steady state conditions at three dose strengths.

Study Overview

• Status: Completed
• Conditions: Healthy; Lower Urinary Tract Symptoms; Benign Prostatic Hyperplasia; Phase 1
• Intervention / Treatment: Drug: EC905; Drug: Tamsulosin HCl; Drug: Solifenacin Succinate

Detailed Description

There will be 3 dose cohorts of 15 subjects each. In Period 1, subjects will be randomized to either receive multiple doses of both tamsulosin HCl and solifenacin succinate as single entity tablets, or the combination tablet EC905. The alternate treatment will be provided in Period 2. The cohorts will be balanced for period effects and first-order carry over effects.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Drente
    • Zuidlaren, Drente, Netherlands, 9471 GP
      • Site NL1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body Mass Index between 18.5 and 30.0 kg/m2.

Exclusion Criteria:

• Known or suspected hypersensitivity to tamsulosin HCl, solifenacin succinate, EC905 or any of the components of the formulations used.
• Any of the liver function tests above the upper limit of normal at repeated measurements.
• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any other drug (excluding non-active hay fever).
• Subject is at risk of urinary retention based on medical history.
• A planned cataract surgery within 30 days after completion of the study.
• Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests.
• Abnormal pulse rate and/or blood pressure measurements at the pre-study visit as follows: pulse rate <40 or >90 bpm; mean systolic blood pressure >160 mmHg; mean diastolic blood pressure >100 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically).
• A marked baseline prolongation of QT/QTc interval after repeated measurements of 450 ms, a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
• Use of any prescribed or OTC (over-the counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day).
• Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
• Any use of drugs of abuse within 3 months prior to admission to the Clinical Unit.
• History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the Clinical Unit.
• History of drinking more than 21 units of alcohol per week (1 unit = 270 cc of beer or 40 cc of spirits or 1 glass of wine) within 3 months prior to admission to the Clinical Unit.
• Donation of blood or blood products within 3 months prior to admission to the Clinical Unit.
• Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.
• Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study, provided that the clinical study did not entail a biological compound with a long terminal half-life. An exception is (partly) participation in Astellas study 905-CL-071, provided a washout of at least 12 days is considered prior to re-enrolment.
• Employee of the Astellas Group or CRO involved in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Tamsulosin HCl and Solifenacin Succinate; Participants will receive daily doses of tamsulosin HCL and Solifenacin Succinate (3 dose strengths) as single tablets.	Drug: Tamsulosin HCl; Oral; Other Names: Omnic OCAS®; Drug: Solifenacin Succinate; Oral; Other Names: Vesicare®
ACTIVE_COMPARATOR: EC905 (tamsulosin HCI and solifenacin succinate); Participants will receive a fixed combination tablet (3 dose strengths).	Drug: EC905; Oral; Other Names: Vesomni®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of tamsulosin HCl and solifenacin succinate in plasma: AUCtau	AUCtau: area under the concentration - time curve (AUC) during the time interval between consecutive dosing	Day 12
PK of tamsulosin HCl and solifenacin succinate in plasma: Cmax	Cmax: maximum concentration	Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile assessed by adverse events, physical examination and vital signs, routine safety laboratory tests, and 12-lead ECG	Vital signs include blood pressure, pulse rate. Safety laboratory test includes urinalysis, hematology, and biochemistry. ECG: Electrocardiogram	Day 0 up to and including the post study visit (the PSV is scheduled between 7 to 14 days after (early) discharge on study day 13)
PK profile Ctrough	Ctrough: Trough concentration	Day 10, 11, 12, 13
PK profile PTR	PTR: Peak Trough Ratio	Day 12
PK profile Tmax	Tmax: Time to attain Cmax	Day 12

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Investigators: Study Director: Director Medical Sciences, Astellas Pharma Europe B.V.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: December 16, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (ESTIMATE): December 18, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 16, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Urinary incontinence; Tamsulosin hydrochloride; Overactive bladder; Solifenacin succinate; Bladder outlet obstruction; Omnic OCAS®; Vesicare®
• Additional Relevant MeSH Terms: Pathologic Processes; Urological Manifestations; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin; Solifenacin Succinate
• Other Study ID Numbers: 905-CL-071; 2007-005155-41 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED