Study to Evaluate the Effect of Solifenacin and Mirabegron on the Digoxin Concentrations in Blood in Healthy Subjects

NCT02127034 | Completed Phase 1

• 2 other identifiers: 178-CL-1072013-004222-28
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of steady state solifenacin and mirabegron on the pharmacokinetics of co-administered steady state digoxin. This study will also evaluate the safety and tolerability of the combined steady state administration of solifenacin, mirabegron and digoxin.

Conditions

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

Keywords

Healthy subjects; Mirabegron; Solifenacin; Digoxin

Outcome Measures

Primary Outcomes (2)

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

  Maximum concentration (Cmax)

  Day 10

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

  Area under the curve over a dosing interval (AUCtau)

  Day 10

Secondary Outcomes (8)

• Pharmacokinetic parameter for digoxin (plasma): Ctrough

  Days 7, 8 and 9 in each investigational period

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

  Days 10 in each investigational period

• Pharmacokinetic parameter for digoxin (urine): Aetau, CLR, Aetau%

  Day 10 in each investigational period

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

  Days 7, 8 and 9 (1 investigational period per sequence only)

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

  Day 10 (1 investigational period per sequence only)

Study Arms (2)

Digoxin / digoxin + solifenacin and mirabegron

EXPERIMENTAL

Digoxin alone then followed by digoxin with solifenacin and mirabegron

Drug: Mirabegron; Drug: Solifenacin; Drug: Digoxin

Digoxin + solifenacin and mirabegron / digoxin

EXPERIMENTAL

Digoxin with solifenacin and mirabegron then followed by digoxin alone

Drug: Mirabegron; Drug: Solifenacin; Drug: Digoxin

Interventions

Mirabegron DRUG

oral

Also known as: Myrbetriq, Betmiga, Betamis

Digoxin + solifenacin and mirabegron / digoxin; Digoxin / digoxin + solifenacin and mirabegron

Solifenacin DRUG

oral

Also known as: solifenacin succinate, Vesikur, Vesicare

Digoxin + solifenacin and mirabegron / digoxin; Digoxin / digoxin + solifenacin and mirabegron

Digoxin DRUG

oral

Also known as: Lenoxin

Digoxin + solifenacin and mirabegron / digoxin; Digoxin / digoxin + solifenacin and mirabegron

Eligibility Criteria

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

You may qualify if:

• Subject has a body mass index range of 20.0 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg \[screening\].
• Female subject must either:
• Be of non-child bearing potential:
• post-menopausal (defined as at least 1 year without any menses) prior to screening, or
• documented surgically sterile
• Or, if of childbearing potential,
• Agree not to try to become pregnant during the clinical study and for 28 days after the final study drug administration, and
• must have a negative urine/serum pregnancy test at screening and day -1,and
• if heterosexually active, agree to consistently use 2 forms of highly effective birth control starting at screening and throughout the clinical study period and for 28 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the clinical study period, and for 28 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the clinical study period, and for 28 days after the final study drug administration.
• Male 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 (1 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.
• Male 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 participating in the present clinical study, defined as signing the informed consent form (ICF) until completion of the last study visit.

You may not qualify if:

• Female subject who has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to solifenacin succinate, mirabegron, digoxin or any components of the formulations used.
• Subject has any of the liver function tests (LFTs) (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], GGT, total bilirubin \[TBL\]) above 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/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to day -1.
• Subject has any clinically significant abnormality following the Investigator's review of the physical examination, ECG (e.g., any level of sinus node disease or atrioventricular defect) and protocol defined clinical laboratory tests (e.g., electrolyte abnormalities such as hypokalemia) at screening or day -1.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, 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 a mean heart rate (HR) of \< 50 or \> 90 beats per minute (bpm); mean systolic BP \>140 mmHg; mean diastolic BP \> 90 mmHg at day-1 (vital sign measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically).
• Subject has a mean QTc(F) interval of \> 430 ms (for males) and \> 450 ms (for females) at day-1. If the mean QTc(F) exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives abnormal result the subject should be excluded.
• 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 has any clinically significant history of or risk of urinary retention, severe gastrointestinal condition (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma.
• Subject uses any prescribed or non-prescribed drugs (including vitamins, hormone replacement therapy or 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.
• Subject has a history of drinking more than 21 units (14 units for females) 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.
• Subject consumes grapefruit juice (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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Parexel International GmbH

Berlin, 14050, Germany

Location

MeSH Terms

Interventions

mirabegron; Solifenacin Succinate; Digoxin

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Clinical Research Physician

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: April 30, 2014
• Study Start: March 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: July 11, 2014

Record last verified: 2014-07

Locations

DE (1)