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Healthy SubjectsPhase 1NCT02127034

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

A Phase 1 study testing Mirabegron, Solifenacin and Digoxin in people with Healthy Subjects and Pharmacokinetics, run by Astellas Pharma Europe B.V. at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
What is being tested?
Mirabegron, Solifenacin and Digoxin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteGermany
Study dates
Mar 2014to Jun 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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,
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit.
  • Subject regularly uses of any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the clinical unit.
  • Subject has significant blood loss, donated 1 unit (500 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on day -1.
  • Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibodies, hepatitis A virus (HAV) antibodies (Immunoglobulin M [IgM]), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) 1+2 antibodies.
  • Subject participated in any clinical study or has been treated with any investigational drugs within 28 days prior to screening.
  • Subject is a vulnerable subject (e.g., subject kept in detention).
  • Subject is an employee of the Astellas Group or Contract Research Organization (CRO) involved in the clinical study.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Parexel International GmbH

    Berlin, 14050

Other trials in Germany

About this study

Official title: A Phase 1 Study to Evaluate the Effect of Steady State Solifenacin and Mirabegron on the Steady State Pharmacokinetics of Digoxin in Healthy Subjects

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.

Read the detailed description

This study is comprised of two study sequences with 2 investigational periods in each sequence. There will be a wash-out period between each investigational period. Patients will be admitted to the clinic until discharged after each investigational period.

Being tested
Mirabegron, Solifenacin, Digoxin
Keywords
Healthy subjects, Mirabegron, Solifenacin, Digoxin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MirabegronDrug

    Also called Myrbetriq, Betmiga, Betamis

    oral

  • SolifenacinDrug

    Also called solifenacin succinate, Vesikur, Vesicare

    oral

  • DigoxinDrug

    Also called Lenoxin

    oral

Study groups in NCT02127034
Study groupRoleWhat they receive
Digoxin / digoxin + solifenacin and mirabegronExperimentalDigoxin alone then followed by digoxin with solifenacin and mirabegron
Receives: Drug: Mirabegron; Drug: Solifenacin; Drug: Digoxin
Digoxin + solifenacin and mirabegron / digoxinExperimentalDigoxin with solifenacin and mirabegron then followed by digoxin alone
Receives: Drug: Mirabegron; Drug: Solifenacin; Drug: Digoxin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Maximum concentration (Cmax)

    Measured: Day 10

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

    Area under the curve over a dosing interval (AUCtau)

    Measured: Day 10

Secondary outcomes (8)

  1. Pharmacokinetic parameter for digoxin (plasma): Ctrough

    Concentration immediately prior to dosing at multiple dosing (Ctrough)

    Measured: Days 7, 8 and 9 in each investigational period

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

    Time after dosing when Cmax occurs (tmax), apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F), Peak-through ratio (PTR)

    Measured: Days 10 in each investigational period

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

    Cumulative amount of drug excreted into urine, feces or bile from the time of dosing to the start of the next dosing interval (Aetau), renal clearance (CLR), percent of drug dose excreted into urine, feces or bile (Aetau) over the time interval between consecutive dosing (Aetau%)

    Measured: Day 10 in each investigational period

  4. Pharmacokinetic parameter for solifenacin and mirabegron (plasma): Ctrough

    Concentration immediately prior to dosing at multiple dosing (Ctrough)

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

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

    Maximum concentration (Cmax), Area under the curve over a dosing interval (AUCtau), Time after dosing when Cmax occurs (tmax), apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F)

    Measured: Day 10 (1 investigational period per sequence only)

  6. Pharmacokinetic parameter for solifenacin and mirabegron (plasma): Cpredose

    Concentration immediately prior to the first dose (Cpredose)

    Measured: Day 1 (1 investigational period for only 1 treatment sequence)

  7. Genotyping for CYP2D6

    Measured: Day 1

  8. Safety as assessed by adverse events, physical examination, vital signs, 12-lead ECG and laboratory tests

    Measured: Up to Day 11 in each investigational period (and at end of study visit, up to 9 days after)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionJun 2014
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02127034
Sponsor's protocol ID
178-CL-107
Other IDs
2013-004222-28
Status last verified
Jul 2014
First submitted
29 Apr 2014
Last updated
11 Jul 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Mirabegron, Solifenacin and Digoxin in people with Healthy Subjects and Pharmacokinetics, run by Astellas Pharma Europe B.V. at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic parameter for digoxin (plasma) in the absence and presence of solifenacin and mirabegron: Cmax (time frame: Day 10). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02127034.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2014.

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