Study to Evaluate the Effect of Solifenacin and Mirabegron on the Tamsulosin Hydrochloride (HCl) Concentrations in Blood in Healthy Male Subjects

NCT02169713 | Completed Phase 1

• 2 other identifiers: 178-CL-1092013-004230-15
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of solifenacin and mirabegron on the concentrations of tamsulosin HCl after combined dosing. This study will also evaluate the safety and tolerability of the combined administration of solifenacin, mirabegron and tamsulosin HCl.

Conditions

Healthy Subjects; Pharmacokinetics; Drug-Drug Interaction (DDI)

Keywords

Healthy subjects; Mirabegron; Solifenacin; Tamsulosin HCl

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic parameter for tamsulosin HCl (plasma) in the absence and presence of solifenacin and mirabegron: Cmax

  Maximum concentration (Cmax)

  Day 14 in each investigational period

• Pharmacokinetic parameter for tamsulosin HCl (plasma) in the absence and presence of solifenacin and mirabegron: AUCtau

  Area under the curve over a dosing interval (AUCtau)

  Day 14 in each investigational period

Secondary Outcomes (4)

• Pharmacokinetic parameter for tamsulosin HCl (plasma): Ctrough

  Days 11, 12 and 13 in each investigational period

• Pharmacokinetic parameter for tamsulosin HCl (plasma): tmax, CL/F, PTR

  Day 14 in each investigational period

• Pharmacokinetic parameter for solifenacin and mirabegron (plasma): Ctrough

  Days 11, 12 and 13 in each investigational period

• Pharmacokinetic parameter for solifenacin and mirabegron (plasma): Cmax, AUCtau, tmax, CL/F

  Day 14 in each investigational period

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

Tamsulosin HCl alone (with matching placebo for solifenacin and mirabegron) then followed by tamsulosin HCl with solifenacin and mirabegron

Drug: Mirabegron; Drug: Solifenacin succinate; Drug: Tamsulosin HCl; Drug: Placebo

Treatment Sequence 2

EXPERIMENTAL

Tamsulosin HCl with solifenacin and mirabegron then followed by tamsulosin HCl alone (with matching placebo for solifenacin and mirabegron)

Drug: Mirabegron; Drug: Solifenacin succinate; Drug: Tamsulosin HCl; Drug: Placebo

Interventions

Mirabegron DRUG

Oral

Also known as: Myrbetriq, Betmiga, Betanis

Treatment Sequence 1; Treatment Sequence 2

Solifenacin succinate DRUG

Oral

Also known as: solifenacin, Vesikur, Vesicare

Treatment Sequence 1; Treatment Sequence 2

Tamsulosin HCl DRUG

Oral

Also known as: Flomax

Treatment Sequence 1; Treatment Sequence 2

Placebo DRUG

Oral

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a body mass index range of 18.5 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg \[screening\].
• Subject and their female spouse/partners who are of childbearing potential must be using a highly effective form of contraception consisting of 2 forms of birth control (one of which must be a barrier method) starting at screening and continue throughout the clinical study period and for 90 days after the final study drug administration.
• Subject must not donate sperm starting at screening and throughout the clinical study period and for 90 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while participation in the present clinical study, defined as signing the informed consent form until completion of the last clinical study visit.

You may not qualify if:

• Subject has a known or suspected hypersensitivity to solifenacin succinate, mirabegron, tamsulosin HCl or any components of the formulations used including sulfa allergies.
• Subject has any of the liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, gamma-glutamyl transferase and/or total bilirubin \[TBL\]) above 1.5 of the upper limit of normal (ULN). In such a case the assessment may be repeated once \[day-1\].
• Subject has any clinically significant history of allergic conditions.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy, as judged by the Medical Investigator.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to day -2 (admission day).
• Subject has any clinically significant abnormality following the Investigator's review of the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or day -1.
• Subject has a mean pulse rate of \< 50 or \> 90 bpm; mean systolic BP \< 90 mmHg or \> 140 mmHg; mean diastolic BP \< 60 mmHg or \> 90 mmHg at day -1 (vital sign measurements taken in triplicate after subject has been resting in supine position for 10 min; pulse rate will be measured automatically).
• Subject has a mean QTc(F) interval of \> 430 ms (\> 450 for subjects aged 65 and above) at day -1. If the mean QTc(F) exceeds the limits above, 1 additional triplicate ECG can be taken.
• Subject has any clinical significant history of or risk of urinary retention, severe gastrointestinal condition (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma, orthostatic hypotension.
• Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease, or a family history of Long QT Syndrome.
• Subject uses any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies \[e.g., St. John's Wort\]) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day).
• Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit on day -2.
• Subject has a history of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) within 3 months prior to admission to the clinical unit on day -2.
• Subject has consumed grapefruit (more than 3 x 200 mL) or marmalade (more than 3 times), star fruit, Seville oranges or Seville orange juice-containing products in the week prior to admission to the clinical unit until end of study visit (ESV), as reported by the subject.
• Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Parexel International GmbH

Berlin, 14050, Germany

Location

MeSH Terms

Interventions

mirabegron; Solifenacin Succinate; Tamsulosin

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Clinical Research Physician

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2014
• First Posted: June 23, 2014
• Study Start: May 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 29, 2014

Record last verified: 2014-08

Locations

DE (1)