i
Submitted by: Geraldine Guerina 2020-09-15 11:29:10 Last Updated by: Geraldine Guerina 2021-01-29 08:36:45


A Phase 3, Double-Blind, Randomized, Multicenter, Parallel Group, Placebo-controlled Sequential Dose Titration Study to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Pediatric Subjects from 5 to

PHRR200925-002943

178-CL-204

2020-CT0558

A Phase 3, Double-Blind, Randomized, Multicenter, Parallel Group, Placebo-controlled Sequential Dose Titration Study to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Pediatric Subjects from 5 to

This study is a double-blind, randomized, multicenter, parallel group, placebo-controlled sequential dose titration study to evaluate efficacy, safety and pharmacokinetics of mirabegron in pediatric subjects with OAB. Subjects will have to receive 4 weeks of urotherapy prior to randomization.

Planned total number of study sites include approximately 50 study sites across Europe, Latin America, Africa, Middle East and Asia-Pacific.

The study consists of 3 periods with a total duration of 18 weeks.

  • A Screening period/urotherapy (4 weeks)
  • A Double-blind, placebo-controlled period (12 weeks)
  • A Follow-up period (2 weeks)

An independent Data and Safety Monitoring Board (DSMB) will be established. A separate charter will describe the responsibilities of the DSMB.

Start Date Duration in Months Target Completion Date Actual Completion Date
2021-01-26 30 2023-07-26 0000-00-00

Ongoing

Institution Classification Region LTO #
Astellas Pharma Global Development, Inc. Private Business United States of America N/A
Institution Classification Region LTO #
PAREXEL Clinical Research (Philippines) Ltd. Corp. Private Business NCR LTO-3000006258189
Institution Region
Astellas Pharma Global Development, Inc. United States of America
Name E-Mail Institution and Institution Address
Adrian Nolasco Adrian.Nolasco@parexel.com 15th Floor, Philam Life Tower, 8767 Paseo de Roxas, Makati City
Name E-Mail Institution and Institution Address
Astellas Pharma Europe B.V., Global Development Operations CTU@astellas.com Sylviusweg 62 Leiden 2333 BE Netherlands
Name Expertise Affiliation
Carlo Bisnar, MD Urologist National Children's Hospital
David Bolong, MD Urologist Philippine Children's Medical Center
John Mata, MD Urologist Perpetual Succour Hospital
Jun Dy, MD Urologist St. Luke's Medcal Center Quezon City
Oscar Escudero Jr., MD Urologist Davao Doctors Hospital
Remedios Garcia-Eulalia, MD Pediatrician Angeles University Foundation Medical Center
Project Location Institutional Ethics Review Board
National Children's Hospital National Children’s Hospital Institutional Ethics Committee/ Independent Review Board
Philippine Children's Medical Center Philippine Children's Medical Center IRB - Ethics Committee
Perpetual Succour Hospital Perpetual Succour Hospital Institutional Ethics and Review Board
St. Luke's Medcal Center Quezon City N/A
Davao Doctors Hospital Davao Doctors Hospital Ethics Review Committee
Angeles University Foundation Medical Center Angeles University Foundation Medical Center Institutional Ethics Review Committee

Overactive Bladder

To evaluate the efficacy of mirabegron in children (5 to

Endpoint: Change from baseline at the end of the 12-week treatment period: Mean number of micturitions per 24 hours

1. To evaluate the efficacy of mirabegron in children (5 to

Endpoint: Change from baseline at the end of the 12-week treatment period: (a) Mean volume voided per 24 hours  (b) Maximum volume voided (c) Mean number of daytime incontinence episodes per 24 hours (d) Mean number of nighttime incontinence episodes per 24 hours (e) Mean number of daytime micturitions per 24 hours

Number of dry (incontinence-free) days per 7 days at the end of the 12-week treatment period

2. To evaluate the safety and tolerability of mirabegron in pediatric subjects with Overactive bladder

Endpoint: Nature, frequency and severity of Adverse Events; Clinical laboratory tests (hemotology, biochemistry and urinalysis); Vital signs (blood pressure and pulse); Routine 12-lead Electrocardiogram; Post void residual (PVR) volume; Acceptability and palatability questionnaire

3. To evaluate the pharmacokinetics after multiple dose administration of mirabegron in pediatric subjects with Overactive bladder

Endpoint: Appropriate pharmacokinetic parameters will be calculated based on the population pharmacokinetic model used

 

Recruiting

  • Belgium
  • Canada
  • Denmark
  • France
  • Germany
  • Italy
  • Malaysia
  • Mexico
  • Netherlands
  • Norway
  • Philippines
  • Poland
  • Russia
  • Serbia
  • South Africa
  • South Korea
  • Spain
  • Turkey
  • Ukraine
  • United Kingdom

Clinical Trial

178-CL-204

20200721134058

2020-09-11

0000-00-00

13

Unspecified

Unspecified

26 Jan 2021

Inclusion Criteria

Subject is eligible for the study if all of the following apply:

Inclusion at Visit 1/Week -4 (Screening)

1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) - approved written informed consent/assent and privacy language as per national regulations (e.g., General Data Protection Regulations for European Union study sites) must be obtained from the subject and/or from the subject's parent(s)/legal guardian(s) prior to any study-related procedures (including withdrawal of prohibited medication, if applicable); assent by the subject is obtained as required by local law.

2. Subject has OAB defined according to the ICCS criteria.

3. Subject is a male or female between 5 to < 18 years of age, at screening.

4. Subject weighs at least 11 kg at screening.

5. Subject is able to take the IP in accordance with the protocol.

6. Subject agrees to drink an adequate fluid volume during urine collection weekends, as instructed by the investigator.

7. Subject and subject's parent(s)/legal guardian(s) agree that the subject will not participate in another interventional study while participating in the present study.

8. Subject and subject's parent(s)/legal guardian(s) are willing and able to comply with the study requirements and with the concomitant medication restrictions.

9. Female subject is not pregnant (see [Appendix 12.3 Contraception Requirements]) and at least 1 of the following conditions apply:

a. Not a woman of childbearing potential (WOCBP) (see [Appendix 12.3 Contraception Requirements]).

b. WOCBP who agrees to follow the contraceptive guidance (see [Appendix 12.3 Contraception Requirements]) from the time of informed consent/assent through at lease 30 days after final IP administration

10. Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.

11. Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.

12. Male subject with female partner(s) of child bearing potential (including breastfeeding partner[s]) must agree to use contraception (see [Appendix 12.3 Contraception Requirements]) throughout the treatment period and for 30 days after final IP administration

13. Male subject must not donate sperm during the treatment period and for 30 days after final IP administration

14. Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.

Additional Inclusion at Visit 3/Week 0 (Baseline)

15. Subject must have a micturition frequency of at least 8 times (on average) per day, in the 7 days prior to visit 3/week 0 (baseline), as recorded in the bladder e-diary.

16. Subject must have at least 1 daytime incontinence episode (on average) per day, during the 7-day period before visit 3/baseline, as recorded in the bladder e-diary.

17. Subject whose symptoms are not satisfactorily controlled with urotherapy and still fulfills the inclusion/exclusion criteria will enter the study.

Exclusion Criteria

Subject will be excluded from participation in this study if any of the following apply:

Exclusion at Visit 1/Week -4 (Screening)

1. Subject has extraordinary daytime only urinary frequency according to the ICCS definition.

  • This applies to a toilet-trained child who has the frequent need to void that is associated with small micturition volumes solely during the day.
  • The daytime voiding frequency is at least once per hour with an average voided volume of < 50% of expected bladder capacity (EBC) (typically 10% to 15%)
  • Incontinence is rare and nocturia is absent.

2. Subject has no uroflow indicative of pathology other than OAB.

3. Subject has monosymptomatic enuresis

4. Subject has dysfunctional voiding

5. Subject has bladder outlet obstruction, except if successfully treated

6. Subject has anatomical anomalies (surgically treated or untreated) that affect lower urinary tract function.

7. Subject with hematuria on dipstick test. In the case of hematuria on dipstick test in a female during menstruation, the test can be repeated before randomization (after the end of menstruation).

8. Subject with diabetes insipidus

9. Subject has kidney or bladder stones.

10. Subject has suffered from chronic UTI or has had more than 3 UTIs in the 2 months prior to visit 1/week -4 (screening).

11. Subject has pulse > 99th percentile for age

12. Subject has stage 2 hypertension or subject has stage 1 hypertension that is not well controlled, as defined by the 2017 American Academy of Pediatrics Clinical Practice Guidelines.

13. Subject has QTcF>440 msec on screening ECG or a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS] or family history of LQTS or exercise-induced syncope)

14. Subject's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is ≥ 2 x upper limit of normal (ULN) or total bilirubin (TBL) is ≥ 1.5 X ULN according to age and sex (subjects with Gilbert's syndrome are excepted from the bilirubin threshold).

15. Subject has mild or moderate renal impairment (estimated glomerular filtration rate according to the modified Schwartz of < 60 mL/min per 1.73 m2).

16. Subject has a symptomatic (symptoms can include pain, fever, hematuria, new onset foul-smelling urine) UTI. Note: if the UTI is treated successfully (clinical recovery: confirmed by dipstick test and repeated dipstick test after 14 days [both should be negative]), the subject can be rescreened.

17. Subject has a history or presence of any malignancy.

18. Subject uses any drugs that are sensitive cytochome P450 2D6 (CYP2D6) substrates with a narrow therapeutic index or sensitive P-glycoprotein(P-gp) substrates after the start of washout

19. Subject is using or has used prohibited prior and/or concomitant medication(s) [Appendix 12.6 List of Excluded Concomitant Medications]

20. Subject has known or suspected hypersensitivity to mirabegron or any components of the formulations used

21. Subject has participated in another clinical study (and/or subject has received any investigational therapy within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1/week -4 (screening)

22. Subject received urinary catheterization within 2 weeks prior to screening.

23. Subject has constipation as defined by the Rome IV criteria that cannot be successfully treated prior to study entry.

24. Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.

25. Subject has any condition, which in the opinion of the investigator, makes the subject unsuitable for study participation.

 Additional Exclusion at Visit 3/Week 0 (Baseline)

26. Subject has extraordinary daytime only urinary frequency according to the ICCS definition based on the bladder e-diary.

27. Subject has monosymptomatic enuresis confirmed by the bladder e-diary

28. Subject has a maximum voided volume (morning volume excluded) > EBC for age ([age+1] x 30) in mL, based on the bladder e-diary

29. Subject has polyuria defined as voided urine volumes of >40mL/kg baseline body weight during 24 hours or >2.8 L urine for a child weighing ≥ 70 kg (ICCS definition) [Austin et al, 2014], based on bladder e-diary

30. Subject has PVR volume >20mL (lowest PVR volume result) as measured by ultrasonography.

31. Subject suffers from a symptomatic (symptoms can include pain, fever, hematuria, new onset foul-smelling urine) UTI. Note: if a symptomatic UTI is present, all visit 3/week 0 (baseline) assessments must be postponed until the UTI is successfully treated (clinical recover: confirmed by dipstick test and repeated dipstick test after 14 days [both should be negative]), and the urotherapy should continue. The postponed visit 3/week 0 (baseline) should be within 14 days of the intended visit 3/week 0 (baseline).

32. Subject with hematuria on dipstick test. In the case of hematuria on dipstick test in a female during menstruation, the test can be repeated before randomization (after the end of menstruation).

33. Subject has a pulse > 99th percentile for age.

34. Subject has stage 2 hypertension or subject has stage 1 hypertension that is not well controlled, as defined by the 2017 American Academy of Pediatrics Clinical Practice Guidelines.

35. Any reason, in the opinion of the investigator, that makes the subject unsuitable for study participation.

Interventional

Mirabegron

Mirabegron, a beta 3-AR agonist, represents a class of drugs for treatment of Overactive Bladder (OAB) with a direct mechanism of action. Mirabegron is currently available as 25 mg and 50 mg tablets. An oral suspension is also being investigated for the treatment of OAB and NDO in the pediatric population.

Date Amendment Classification Reason
2020-09-04 Amendments related to the trial arrangements Change of the principal investigator or addition of new ones
2020-11-27 Amendments related to the trial arrangements Change of the principal investigator or addition of new ones
2020-11-27 Amendments related to the trial arrangements Change of the trial site or addition of new site
2021-01-11 Amendments related to the protocol Additional Informed Consent Form (Cebuano-Davao), Additional Patient Materials (Cebuano-Davao), Additional Site and Principal Investigator (Dr. Escudero)

Randomized

Double Blind

Unspecified

Parallel

To evaluate the efficacy of mirabegron in children (5 to

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
©2021 HERDIN PLUS. All rights reserved. | Contact Us | Keep up to date