Overview

Efficacy and Safety Study of GSK1358820 in Japanese Patients With Urinary Incontinence Due to Neurogenic Detrusor Overactivity

Status:
Completed
Trial end date:
2018-12-20
Target enrollment:
0
Participant gender:
All
Summary
This study will evaluate the efficacy and safety of GSK1358820 in Japanese patients with neurogenic detrusor overactivity (NDO) with urinary incontinence, whose symptoms have not been adequately managed with medications for urinary incontinence due to NDO. This study consists of a screening phase up to 28 days followed by a double-blind Treatment phase 1 of 12 to 48 weeks wherein subjects will receive a single treatment of either GSK1358820 200 Units (U) injection or placebo injection. After the first treatment, subjects who meet the re-treatment criteria between 12 to 36 weeks can enter an open-label Treatment phase 2 to receive a second treatment with GSK1358820 200 U. Subjects will be permitted to receive re-treatment up to 2 times, and there should be a gap of minimum of 12 weeks since the previous treatment. The duration of overall treatment phases is 48 weeks. The total duration of participation for any subject will not exceed 52 weeks, including screening.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
GlaxoSmithKline
Treatments:
abobotulinumtoxinA
Anesthetics
Botulinum Toxins
Botulinum Toxins, Type A
incobotulinumtoxinA
Neuromuscular Blocking Agents
onabotulinumtoxinA
Criteria
Inclusion Criteria:

- Aged >=20 years at the time of signing the informed consent

- Subject has urinary incontinence as a result of neurogenic detrusor overactivity for a
period of at least 3 months prior to screening as a result of spinal cord injury or
multiple sclerosis, determined by documented subject history. In addition:

1. Spinal cord injury subjects must have a stable neurological injury level C5 or
below occurring >=6 months prior to screening.

2. Multiple sclerosis subjects must be clinically stable in the investigator's
opinion, for >=3 months prior to screening and have an Expanded Disability Status
Scale score <=6.5

- Subject has NDO for a period of at least 3 months prior to screening, determined by
documented subject history. The presence of an involuntary detrusor contractions (IDC)
must also be demonstrated during the urodynamic assessment during the screening period
or Day 1 (prior to randomization).

- Subject has not been adequately managed with one or more medications (i.e.,
anticholinergics or beta-3 adrenergic receptor agonist) for treatment of urinary
incontinence due to NDO . Not adequately managed is defined as:

An inadequate response after at least a 4-week period of medication(s) for urinary
incontinence due to NDO on an optimized dose(s), i.e., subject is still incontinent despite
medication(s) for urinary incontinence due to NDO, or Limiting side effects (i.e.,
condition that subject reduced dosage or discontinued the medication due to side effect)
after at least a 2-week period of medication(s) for urinary incontinence due to NDO on an
optimized dose(s)

- Subject has >=6 episodes of urinary incontinence, with no more than one urgency
incontinence-free day in the 3-day subject bladder diary completed during the
screening phase

- Subject currently uses or is willing to use clean intermittent catheterization (CIC)
to empty the bladder (indwelling catheter is not permitted). Subjects currently on CIC
should be willing to maintain a CIC schedule of at least 3 times per day throughout
the study. Caregiver may perform CIC.

- Body weight >=40 kilogram (kg) at screening

- Males or females:

1. Male subjects with female partners of child bearing potential must comply with
the following contraception requirements from the time of first dose of study
medication until the study exit:

- Vasectomy with documentation of azoospermia.

- Male condom plus partner use of one of following the contraceptive
options:Intrauterine device or intrauterine system that meets the standard
operating procedure (SOP) effectiveness criteria including a <1% rate of
failure per year, as stated in the product label; or oral contraceptive,
either combined or progestogen alone These allowed methods of contraception
are only effective when used consistently, correctly and in accordance with
the product label. The investigator is responsible for ensuring that
subjects understand how to properly use these methods of contraception

2. Female subject is eligible to participate if she is not pregnant (as confirmed by
a negative urine or serum human chorionic gonadotrophin [hCG] test), not
lactating, and at least one of the following conditions applies:

• Non-reproductive potential defined as: Pre-menopausal females with one of the
following: Documented tubal ligation, Documented hysteroscopic tubal occlusion
procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy,
Documented Bilateral Oophorectomy.

Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone
replacement therapy (HRT) and whose menopausal status is in doubt will be
required to use one of the highly effective contraception methods if they wish to
continue their HRT during the study. Otherwise, they must discontinue HRT to
allow confirmation of post-menopausal status prior to study enrollment.

• Reproductive potential and agrees to follow one of the options listed below in
the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding
Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days
prior to the first dose of study medication and until the study exit. This list
of highly effective methods (approved in Japan) is provided below, and it does
not apply to FRP with same sex partners, when this is their preferred and usual
lifestyle or for subjects who are and will continue to be abstinent from
penile-vaginal intercourse on a long term and persistent basis: Intrauterine
device or intrauterine system that meets the SOP effectiveness criteria including
a <1% rate of failure per year, as stated in the product label; Oral
Contraceptive, either combined or progestogen alone; Male partner sterilization
with documentation of azoospermia prior to the female subject's entry into the
study, and this male is the sole partner for that subject.

These allowed methods of contraception are only effective when used consistently,
correctly and in accordance with the product label. The investigator is
responsible for ensuring that subjects understand how to properly use these
methods of contraception.

- Subject has given signed informed consent, including compliance with the requirements
and restrictions listed in the consent form and in this protocol (e.g., complete
bladder diaries and questionnaires, is able to collect volume voided per micturition
measurements over a 24-hour period, and attend all study visits in the opinion of the
investigator(or subinvestigator).

Exclusion Criteria:

- Subject has a history or evidence of any diseases, functional abnormalities or bladder
surgery, other than NDO, that may have affected bladder function including but not
limited to:

1. Bladder stones (including bladder stone surgery) within 6 months prior to
screening or confirmed occurrence of bladder stones at the screening phase

2. Surgery (including minimally invasive surgery) within 1 year of screening for
stress incontinence or pelvic organ prolapse

3. Current use of an electrostimulation/neuromodulation device for treatment of
urinary incontinence. Note: Use of any implantable device is prohibited within 4
weeks prior to initiation of Screening phase and throughout the study period. Use
of any external device is discontinued at least 7 days prior to the start of the
screening phase

4. Current use of a baclofen pump

5. History of interstitial cystitis, in the opinion of the investigator (or
subinvestigator)

6. Past or current evidence of hematuria due to urological/renal pathology or
uninvestigated hematuria. Subjects with investigated hematuria may enter the
study if urological/renal pathology has been ruled out to the satisfaction by the
investigator (or subinvestigator)

7. Past or current history of bladder cancer or other urothelial malignancy,
positive result of urine cytology or uninvestigated suspicious urine cytology
results at the Screening phase. Suspicious urine cytology abnormalities require
that bladder cancer or other urothelial malignancy has been ruled out to the
satisfaction of the investigator according to local site practice.

8. An active genital infection, other than genital warts, either concurrently or
within 4 weeks prior to Screening

9. Male with previous or current diagnosis of prostate cancer or a prostate specific
antigen (PSA) level of >10 nanogram (ng)/milliliter (mL) at Screening. Subjects
with a PSA level of >= 4 ng/mL but <= 10 ng/mL must have prostate cancer ruled
out to the satisfaction of the investigator (or subinvestigator) according to
local site practice.

10. Evidence of urethral and/or bladder outlet obstruction, in the opinion of the
investigator (or subinvestigator)

- Subject has a serum creatinine level >2 times the upper limit of normal (ULN) at
screening

- Alanine aminotransferase (ALT) > 2×ULN; and bilirubin > 1.5×ULN (isolated bilirubin
>1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at
screening

- Subject has current active liver or biliary disease (with the exception of Gilbert's
syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per
investigator assessment). Notes:

1. Stable chronic liver disease should generally be defined by the absence of
ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric
varices, or persistent jaundice, or cirrhosis

2. Chronic stable hepatitis B and C (example, presence of hepatitis B surface
antigen [HBsAg] or positive hepatitis C antibody [HCVAb] test result within 3
months prior to first dose of study treatment) are acceptable if subject
otherwise meets entry criteria

- QTc >450 milliseconds (msec) or QTc >480 msec in subjects with Bundle Branch Block
from the result of ECG at screening. Notes:

1. The QTc is the QT interval corrected for heart rate according to Bazett's formula
(QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or
manually over-read

2. The specific formula that will be used to determine eligibility and
discontinuation for an individual subject should be determined prior to
initiation of the study. In other words, several different formulae cannot be
used to calculate the QTc for an individual subject and then the lowest QTc value
used to include or discontinue the subject from the trial

- Subject has hemophilia or other clotting factor deficiencies or disorders that cause
bleeding diathesis

- Subject changes or initiates or discontinues anticholinergic, beta-3 adrenergic
receptor agonist or any other medications or therapies to treat urinary incontinence
due to NDO, within 6 days prior to the start of the screening phase

- Subject has been treated with any intravesical pharmacologic agent (e.g., capsaicin,
resiniferatoxin) for urinary incontinence due to NDO within 12 months prior to
initiation of Treatment phase 1 (Week 0)

- Subject has previous or current use of botulinum toxin therapy of any serotype for the
treatment of any urological condition

- Subject has previous use within 12 weeks prior to initiation of Treatment phase 1
(Week 0) or current use of botulinum toxin therapy of any serotype for any
non-urological condition or beauty care

- Subject has been immunized for botulinum toxin of any serotype

- Subject cannot withhold any antiplatelet or anticoagulant therapy or medications with
anticoagulative effects for 3 days prior to initiation of Treatment phase 1 (Week 0).
Some medications may need to be withheld for > 3 days, per clinical judgment of the
investigator (or subinvestigator).

- Subject without a urinary tract infection (UTI) as determined from the urinalysis or
urine culture and/or investigator opinion, has not initiated prophylactic antibiotic
medication 1 to 3 days prior to the initiation of Treatment phase 1 (Week 0). Subject
with a UTI as determined from the urinalysis or urine culture and/or investigator
opinion, has not initiated antibiotic medication at least 5 days prior to the
initiation of Treatment phase 1 (Week 0)

- Subject is symptomatic for UTI on day of treatment

- Subject has a history of sensitivity to any of the study medications, medications used
in the study (including anesthesia), or their components or a history of drug or other
allergy that, in the opinion of the investigator or Medical Monitor, contraindicates
their participation

- Subject has any medical condition that may put them at increased risk with exposure to
GSK1358820 including diagnosed myasthenia gravis, Eaton-Lambert syndrome, or
amyotrophic lateral sclerosis

- Females who are pregnant, nursing or planning a pregnancy during the study

- Subject has a post void residual urine volume above 200 mL for subjects who micturate
or have a mixed catheterization/spontaneous micturition pattern. The post void
residual measurement can be repeated once; the subject is to be excluded if the
repeated measure is above 200 mL.

- Subject has a 24-hour total volume of urine voided >3000 mL of urine collected over 24
consecutive hours during the 3-day bladder diary collection period in the Screening
phase

- Subject is currently participating in or has previously participated in another
therapeutic study within 30 days prior to the start of the Screening phase

- Subject has any condition or situation which, in the investigator's (or
sub-investigator's) opinion, puts the subject at significant risk, may confound the
study results, or may interfere significantly with the subject's participation in the
study.