Register a trial

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02751931


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT02751931
Ethics application status
Date submitted
22/04/2016
Date registered
26/04/2016

Titles & IDs
Public title
Open-label Phase 3 Study With Mirabegron in Children From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity
Scientific title
An Open-label, Baseline-controlled, Multicenter, Phase 3 Dose-titration Study Followed by a Fixed-dose Observation Period to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Children and Adolescents From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity (NDO) on Clean Intermittent Catheterization (CIC)
Secondary ID [1] 0 0
2015-002876-25
Secondary ID [2] 0 0
178-CL-206A
Universal Trial Number (UTN)
Trial acronym
Crocodile
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurogenic Detrusor Overactivity 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mirabegron

Experimental: Children (3 to < 12 Years) - Participants aged 3 to \< 12 years received initial dose of 25 milligram (mg) of mirabegron orally once daily based on weight (pediatric equivalent dose of 25 mg (milligram) \[PED25\]) on day 1. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults \[PED50\], orally once daily based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 end-of-study (EOS) or end-of-treatment (EOT).

Experimental: Adolescents (12 to < 18 Years) - Participants aged 12 to \< 18 years received initial dose of 25 mg of mirabegron orally once daily based on weight \[PED25\] on day 1. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults \[PED50\] orally once daily based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT.


Treatment: Drugs: Mirabegron
Participants received initial dose of 25 mg of mirabegron PED25 orally once daily. At weeks 2, 4 or 8, participants were up-titrated to PED50 based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT. Participants with a body weight \>=35 kg received mirabegron tablets or body weight \<35 kg received mirabegron oral suspension. At week 24, participants on mirabegron oral suspension could switch to tablets if the body weight became \>=35 kg or participants on mirabegron tablets could switch to oral suspension if the body weight became \<35 Kg or participants could switch to either of the dosage form for acceptability reasons after sponsor's prior approval and on a case-by-case basis. Mirabegron extended-release granules were reconstituted with water to prepare a mirabegron oral suspension of 8 mg/mL. Administration was via an oral syringe with a sip of water afterwards.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 24
Timepoint [1] 0 0
Baseline and week 24
Secondary outcome [1] 0 0
Change From Baseline in Bladder Compliance (?V/?P)
Timepoint [1] 0 0
Baseline and weeks 4 and 24
Secondary outcome [2] 0 0
Change From Baseline in Maximum Cystometric Capacity at Week 4
Timepoint [2] 0 0
Baseline and week 4
Secondary outcome [3] 0 0
Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cm H20) Until End of Filling
Timepoint [3] 0 0
Baseline and weeks 4 and 24
Secondary outcome [4] 0 0
Change From Baseline in Detrusor Pressure at End of Filling
Timepoint [4] 0 0
Baseline and weeks 4 and 24
Secondary outcome [5] 0 0
Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20)
Timepoint [5] 0 0
Baseline and weeks 4 and 24
Secondary outcome [6] 0 0
Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Wilcoxon Signed-rank Test Updated Analysis
Timepoint [6] 0 0
Baseline and weeks 4 and 24
Secondary outcome [7] 0 0
Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Paired T-test
Timepoint [7] 0 0
Baseline and weeks 4 and 24
Secondary outcome [8] 0 0
Change From Baseline in Average Catheterized Volume Per Catheterization
Timepoint [8] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [9] 0 0
Change From Baseline in Maximum Catheterized Volume
Timepoint [9] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [10] 0 0
Change From Baseline in Maximum Catheterized Daytime Volume (MCDV)
Timepoint [10] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [11] 0 0
Change From Baseline in Average Morning Catheterized Volume
Timepoint [11] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [12] 0 0
Change From Baseline in Mean Number of Leakage Episodes Per Day
Timepoint [12] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [13] 0 0
Change From Baseline in Mean Number of Leakage Episodes Per Day: Updated Analysis
Timepoint [13] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [14] 0 0
Change From Baseline in Number of Dry Days Per 7 Days (Day and Night Time)
Timepoint [14] 0 0
Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
Secondary outcome [15] 0 0
Change From Baseline in Pediatric Incontinence Questionnaire (PIN-Q) Score
Timepoint [15] 0 0
Baseline and weeks 24 and 52
Secondary outcome [16] 0 0
Change From Baseline in Patient Global Impression of Severity Scale (PGI-S)
Timepoint [16] 0 0
Baseline and weeks 24 and 52
Secondary outcome [17] 0 0
Number of Participants With Clinician Global Impression of Change (CGI-C)
Timepoint [17] 0 0
Weeks 24 and 52
Secondary outcome [18] 0 0
Number of Participants With Study Drug Acceptability for Tablets at Week 4
Timepoint [18] 0 0
Week 4
Secondary outcome [19] 0 0
Number of Participants With Study Drug Acceptability for Tablets at Week 24
Timepoint [19] 0 0
Week 24
Secondary outcome [20] 0 0
Number of Participants With Study Drug Acceptability for Tablets at Week 52
Timepoint [20] 0 0
Week 52
Secondary outcome [21] 0 0
Number of Participants With Study Drug Acceptability for Oral Suspension at Week 4
Timepoint [21] 0 0
Week 4
Secondary outcome [22] 0 0
Number of Participants With Study Drug Acceptability for Oral Suspension at Week 24
Timepoint [22] 0 0
Week 24
Secondary outcome [23] 0 0
Number of Participants With Study Drug Acceptability for Oral Suspension at Week 52
Timepoint [23] 0 0
Week 52
Secondary outcome [24] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [24] 0 0
From the first dose of study drug administration up to end-of-treatment (EoT) (up to week 52)
Secondary outcome [25] 0 0
Maximum Plasma Concentration (Cmax) of Mirabegron
Timepoint [25] 0 0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
Secondary outcome [26] 0 0
Time to Reach Maximum Plasma Concentration of Mirabegron Following Drug Administration (Tmax)
Timepoint [26] 0 0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
Secondary outcome [27] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) for Mirabegron
Timepoint [27] 0 0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
Secondary outcome [28] 0 0
Plasma Concentration of Mirabegron at the End of a Dosing Interval at Steady State (Ctrough)
Timepoint [28] 0 0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
Secondary outcome [29] 0 0
Apparent Total Clearance of Mirabegron From Plasma After Oral Administration (CL/F)
Timepoint [29] 0 0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
Secondary outcome [30] 0 0
Apparent Volume of Distribution After Non-intravenous Administration (Vz/F) of Mirabegron
Timepoint [30] 0 0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.

Eligibility
Key inclusion criteria
* Subject has a body weight of greater than or equal to 11 kg.
* Subject suffers from NDO confirmed by urodynamic investigation at baseline. The diagnosis of NDO must be confirmed by the presence of at least 1 involuntary detrusor contraction > 15 cm H2O from baseline detrusor pressure, and/or a decrease in compliance leading to an increase in baseline detrusor pressure of > 20 cm H2O.
* Subject has been using CIC for at least 4 weeks prior to visit 1/screening.
* Subject has a current indication for drug therapy to manage NDO.
* Subject is able to take the study drug in accordance with the protocol
Minimum age
3 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subject has a known genitourinary condition (other than NDO) that may cause overactive contractions or incontinence or kidney/bladder stones or another persistent urinary tract pathology that may cause symptoms.
* Subject has one of the following gastrointestinal problems: partial or complete obstruction, decreased motility such as paralytic ileus, subjects at risk of gastric retention.
* Subject has a urinary indwelling catheter within 4 weeks prior to visit 1/screening.
* Subject has a surgically treated underactive urethral sphincter
* Subject has vesico-ureteral reflux grade 3 to 5.
* Subject has undergone bladder augmentation surgery.
* Subject receives electrostimulation therapy, if started within 30 days before visit 1/screening or is expected to start during the study period. Subjects who are on an established regimen may remain on this for the duration of the study.
* Subject suffers from a symptomatic urinary tract infection (UTI) at baseline (symptomatic is defined as pain, fever, hematuria, new onset foul-smelling urine). If present at visit 1/screening or diagnosed between visit 1/screening and visit 3/baseline, the UTI should be treated successfully (clinical recovery) prior to baseline. If a symptomatic UTI is present at baseline, all baseline assessments are allowed to be postponed for a maximum of 7 days until the UTI is successfully treated (clinical recovery).
* Subject has a (mean) resting pulse rate > 99th percentile [Fleming et al, 2011].
* Subject has an established hypertension and a systolic or diastolic blood pressure greater than the 99th percentile of the normal range determined by sex, age and height, plus 5mmHg [NIH 2005].
* Subject has a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS]; or family history of LQTS, exercise-induced syncope).
* Subject has severe renal impairment (eGFR according to Larsson equation < 30 mL/min).
* Subject's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is greater than or equal to 2 times the upper limit of normal (ULN) or total bilirubin (TBL) greater than or equal to 1.5 times the ULN according to age and sex.
* Subject has a history or presence of any malignancy prior to visit 1/screening.
* Subject has known or suspected hypersensitivity to mirabegron, any of the excipients used in the current formulations or previous severe hypersensitivity to any drug.
* Subject has participated in another clinical trial (and/or has taken an investigational drug within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1/screening.
* Subject uses any of the following prohibited medications (after start of washout):

* Any medication, other than the study drug used, for the management of NDO;
* Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates
* Any strong CYP3A4 inhibitors if the subject has a mild to moderate renal impairment (eGFR 30 - 89 mL/min).
* Subject has been administered intravesical botulinum toxin; except if given > 4 months prior to visit 1/screening and the subject experiences symptoms comparable to those existing prior to the botulinum toxin injections.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/05/2019
Sample size
Target
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Site AU61002 - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Edegem
Country [2] 0 0
Belgium
State/province [2] 0 0
Gent
Country [3] 0 0
Croatia
State/province [3] 0 0
Zagreb
Country [4] 0 0
Denmark
State/province [4] 0 0
Aarhus N
Country [5] 0 0
Denmark
State/province [5] 0 0
Copenhagen
Country [6] 0 0
Israel
State/province [6] 0 0
Jerusalem
Country [7] 0 0
Jordan
State/province [7] 0 0
Amman
Country [8] 0 0
Jordan
State/province [8] 0 0
Irbid
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Seoul
Country [10] 0 0
Latvia
State/province [10] 0 0
Riga
Country [11] 0 0
Lithuania
State/province [11] 0 0
Kaunas
Country [12] 0 0
Lithuania
State/province [12] 0 0
Vilnius
Country [13] 0 0
Malaysia
State/province [13] 0 0
Georgetown
Country [14] 0 0
Malaysia
State/province [14] 0 0
Kuala Lumpur
Country [15] 0 0
Mexico
State/province [15] 0 0
Mexico City
Country [16] 0 0
Norway
State/province [16] 0 0
Bergen
Country [17] 0 0
Philippines
State/province [17] 0 0
Quezon City
Country [18] 0 0
Poland
State/province [18] 0 0
Gdansk
Country [19] 0 0
Poland
State/province [19] 0 0
Warszawa
Country [20] 0 0
Romania
State/province [20] 0 0
Bucuresti
Country [21] 0 0
Serbia
State/province [21] 0 0
Nis
Country [22] 0 0
Serbia
State/province [22] 0 0
Novi Sad
Country [23] 0 0
Slovakia
State/province [23] 0 0
Bratislava
Country [24] 0 0
Taiwan
State/province [24] 0 0
New Taipei City
Country [25] 0 0
Turkey
State/province [25] 0 0
Ankara
Country [26] 0 0
Turkey
State/province [26] 0 0
Bursa
Country [27] 0 0
Turkey
State/province [27] 0 0
Mersin

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Astellas Pharma Europe B.V.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Astellas Pharma Europe B.V.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Available to whom?
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02751931

Additional trial details provided through ANZCTR
Accrual to date
Recruitment state(s)
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
 
Public notes
Please refer to ClinicalTrials.gov website link (https://clinicaltrials.gov/ct2/show/results/NCT02751931?term=178-cl-206a&draw=2&rank=1) and EU CTR website link (https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-002876-25/results) or the Astellas Website (www.astellasclinicalstudyresults.com) for results.

Contacts
Principal investigator
Title 361 0
Name 361 0
Address 361 0
Country 361 0
Phone 361 0
Fax 361 0
Email 361 0
Contact person for public queries
Title 362 0
Name 362 0
Address 362 0
Country 362 0
Phone 362 0
Fax 362 0
Email 362 0
Contact person for scientific queries
Title 363 0
Name 363 0
Address 363 0
Country 363 0
Phone 363 0
Fax 363 0
Email 363 0