EC905 Pharmacokinetic Profile Study

Phase 1

Completed

• Conditions: Healthy; Phase 1; Benign Prostatic Hyperplasia; Lower Urinary Tract Symptoms
• Interventions: Drug: EC905; Drug: Tamsulosin HCl; Drug: Solifenacin Succinate

• Registration Number: NCT02634489
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

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.

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 Timeline

• Study Start: 2009-03
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Status Verified: 2015-12
• Study First Submitted: 2015-12-16
• Study First Submitted QC: 2015-12-16
• Last Update Submitted: 2015-12-16
• Study First Posted: 2015-12-18
• Last Update Posted: 2015-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
EC905 (tamsulosin HCI and solifenacin succinate)	EC905	Participants will receive a fixed combination tablet (3 dose strengths).
Tamsulosin HCl and Solifenacin Succinate	Tamsulosin HCl	Participants will receive daily doses of tamsulosin HCL and Solifenacin Succinate (3 dose strengths) as single tablets.
Tamsulosin HCl and Solifenacin Succinate	Solifenacin Succinate	Participants will receive daily doses of tamsulosin HCL and Solifenacin Succinate (3 dose strengths) as single tablets.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
PK profile Tmax	Day 12	Tmax: Time to attain Cmax
PK profile PTR	Day 12	PTR: Peak Trough Ratio
Safety profile assessed by adverse events, physical examination and vital signs, routine safety laboratory tests, and 12-lead ECG	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)	Vital signs include blood pressure, pulse rate. Safety laboratory test includes urinalysis, hematology, and biochemistry. ECG: Electrocardiogram
PK profile Ctrough	Day 10, 11, 12, 13	Ctrough: Trough concentration

Trial Locations

Locations (1)

Site NL1; 🇳🇱 Zuidlaren, Drente, Netherlands