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

NCT02849418 | Completed Phase 3 Results

• 1 other identifier: 204948
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Urinary Bladder, Overactive

Keywords

Botulinum toxin type A; Urinary Incontinence; Neurogenic Detrusor Overactivity

Outcome Measures

Primary Outcomes (1)

• Treatment Phase 1 (Treatment Cycle 1)- Change From Baseline in the Daily Average Number of Urinary Incontinence Episodes at Week 6

  Participants were instructed to enter data in the bladder diary over 3 consecutive days. For Baseline and post-treatment visits, analysis was based on the diary data collected during a 3-day interval for each visit. Each 3-day interval consisted of 3 consecutive 24-hour periods, with the first period starting from the time of the first urinary episode on the first of the 3 days. A valid diary day was defined as any of the three 24-hour periods with 2 or more any type of urinary incontinence episodes. Data collected from a 24-hour period with less than 2 urinary incontinence episodes (i.e., an invalid diary day) were set to missing. Baseline was defined as the latest pre-dose 3-day diary which has at least one valid diary day. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. Adjusted mean and standard error of adjusted mean has been reported.

  Baseline (Pre-dose on Day 1) and Week 6 in Treatment Cycle 1

Secondary Outcomes (79)

• Treatment Phase 1 (Treatment Cycle 1)- Change From Baseline in Maximum Cystometric Capacity (MCC) by Urodynamic Assessment at Week 6

  Baseline (Pre-dose on Day 1) and Week 6 in Treatment Cycle 1

• Treatment Phase 1 (Treatment Cycle 1)- Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) (PmaxIDC) by Urodynamic Assessment at Week 6

  Baseline (Pre-dose on Day 1) and Week 6 in Treatment Cycle 1

• Treatment Phase 1 (Treatment Cycle 1)- Change From Baseline in Volume at First IDC (VPmaxIDC) by Urodynamic Assessment at Week 6

  Baseline (Pre-dose on Day 1) and Week 6 in Treatment Cycle 1

• Treatment Phase 1 (Treatment Cycle 1)- Change From Baseline in Maximum Detrusor Pressure During the Storage Phase (PdetMax) by Urodynamic Assessment at Week 6

  Baseline (Pre-dose on Day 1) and Week 6 in Treatment Cycle 1

• Treatment Phase 1 (Treatment Cycle 1)- Change From Baseline in the Daily Average Number of Urinary Incontinence Episodes

  Baseline (Pre-dose on Day 1), Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42 and Week 48 in Treatment Cycle 1

Study Arms (2)

GSK1358820 Injection 200 U

EXPERIMENTAL

Subjects will receive a single treatment with 200 U GSK1358820 injection (30 mL of study drug will be administered as 30 injections, each of 1.0 mL) in the detrusor of bladder, using cystoscopy and under local anesthesia. General anesthesia may be used excluding neuromuscular blocking agents. If the criteria for re-treatment between 12 to 36 weeks after first treatment are met, subjects will receive a second treatment with GSK1358820. Following this, subjects could receive another re-treatment up to 36 weeks after the first treatment, upon meeting the criteria, provided a minimum of 12 weeks elapse since previous treatment.

Drug: GSK1358820

Placebo Injection

PLACEBO COMPARATOR

Subjects will receive a single treatment with placebo (30 injections, each of 1 mL) in the detrusor of bladder, using cystoscopy and under local anesthesia. General anesthesia may be used excluding neuromuscular blocking agents. If the criteria for re-treatment between 12 to 36 weeks after first treatment are met, subjects will receive treatment with GSK1358820. Following this, subjects could receive another re-treatment up to 36 weeks after the first treatment, upon meeting the criteria, provided a minimum of 12 weeks elapse since previous treatment

Drug: Placebo

Interventions

GSK1358820 DRUG

GSK1358820 injection contains botulinum toxin type A (100 U), sodium chloride (0.9 milligrams \[mg\]), and human serum albumin (0.5 mg). The 30 mL of study drug will be administered as 30 injections each of 1.0 mL, evenly distributed at 30 sites in the detrusor muscle, spaced approximately 1 centimeter (cm) apart. The injection will be administered using cystoscopy and under local anesthesia. General anesthesia may be used excluding neuromuscular blocking agents.

GSK1358820 Injection 200 U

Placebo DRUG

Placebo injection contains sodium chloride (0.9 milligrams \[mg\]); 30 mL of the injection will be injected at 30 sites in the detrusor muscle, spaced approximately 1 centimeter (cm) apart. The injection will be administered using cystoscopy and under local anesthesia. General anesthesia may be used excluding neuromuscular blocking agents

Placebo Injection

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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:
• Bladder stones (including bladder stone surgery) within 6 months prior to screening or confirmed occurrence of bladder stones at the screening phase
• Surgery (including minimally invasive surgery) within 1 year of screening for stress incontinence or pelvic organ prolapse
• 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
• Current use of a baclofen pump
• History of interstitial cystitis, in the opinion of the investigator (or subinvestigator)
• 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)
• 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.
• An active genital infection, other than genital warts, either concurrently or within 4 weeks prior to Screening
• 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.
• 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:
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Aomori, 036-8563, Japan

Location

GSK Investigational Site

Fukuoka, 820-8508, Japan

Location

GSK Investigational Site

Hokkaido, 060-8648, Japan

Location

GSK Investigational Site

Hyōgo, 651-2181, Japan

Location

GSK Investigational Site

Miyagi, 981-8563, Japan

Location

GSK Investigational Site

Nagasaki, 852-8501, Japan

Location

GSK Investigational Site

Okayama, 700-8558, Japan

Location

GSK Investigational Site

Tochigi, 321-0293, Japan

Location

GSK Investigational Site

Yamanashi, 409-3898, Japan

Location

Related Publications (1)

• Honda M, Yokoyama O, Takahashi R, Matsuda T, Nakayama T, Mogi T. Botulinum toxin injections for Japanese patients with urinary incontinence caused by neurogenic detrusor overactivity: Clinical evaluation of onabotulinumtoxinA in a randomized, placebo-controlled, double-blind trial with an open-label extension. Int J Urol. 2021 Sep;28(9):906-912. doi: 10.1111/iju.14602. Epub 2021 Jun 1.

  PMID: 34075630 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder, Overactive; Urinary Incontinence

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urination Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: July 29, 2016
• Study Start: October 11, 2016
• Primary Completion: March 2, 2018
• Study Completion: December 20, 2018
• Last Updated: July 14, 2021
• Results First Posted: July 10, 2019

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

JP (9)