Efficacy and Safety of GSK1358820 in Subjects With Overactive Bladder

NCT02820844 | Completed Phase 3 Results

• 1 other identifier: 204947
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 48

Brief Summary

GSK1358820 is a botulinum neurotoxin A complex that has been approved for the treatment of overactive bladder (OAB) in several countries, however, it has not been approved for OAB treatment in Japan. This study has been planned to evaluate the efficacy and safety of GSK1358820 in Japanese OAB patients with urinary incontinence whose symptoms have not been adequately managed with other medications for OAB. The primary objective of this study is to evaluate the superiority of a single dose treatment of GSK1358820 100 units (U) compared with placebo. The study comprises a screening phase up to 28 days, followed by a double-blind treatment phase of 12 to 48 weeks wherein subjects will receive a single treatment of either GSK1358820 100 U injection or Placebo injection, in a ratio of 1:1, with further stratification within the treatment arms according to the number of urinary urge incontinence episodes during screening. Subjects meeting the criteria for re-treatment will receive a second and third treatment. Each re-treatment will be with open-label GSK1358820 100 U injection, and will be spaced at least 12 weeks from the previous treatment. The total duration of participation for any subject will not exceed 52 weeks, including screening and the 48-week treatment period.

Conditions

Urinary Bladder, Overactive

Keywords

Overactive bladder; Botulinum toxin type A; Urinary incontinence

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 12 After the First Treatment

  Participants were instructed to enter data in a bladder diary over 3 consecutive days within a week prior to each scheduled visit (or within 28 days prior to Day 1), excluding the day of visit (this period was called the '3-day diary collection period'). The daily average of the number of incontinence episodes were calculated using formula; number of "Yes" response to the diary question of accidental urinary leakage divided by number of valid diary days in the visit. Baseline is the latest pre-dose 3- day diary assessment which has at least one valid diary day. Change from Baseline is any visit value minus Baseline value. Adjusted mean and standard error of adjusted mean has been reported.

  Baseline (Pre-dose on Day 1) and Week 12 in Treatment Cycle 1

Secondary Outcomes (118)

• Treatment Phase 1 (Treatment Cycle 1): Change From Baseline in the Average Volume Voided Per Micturition at Week 12 After the First Treatment

  Baseline (Pre-dose on Day 1) and Week 12 in Treatment Cycle 1

• Treatment Phase 1 (Treatment Cycle 1): Changes From Baseline in 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

• Treatment Phase 2 (Treatment Cycle 2): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

  Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18, Week 24, Week 30, and Week 36 in Treatment Cycle 2

• Treatment Phase 2 (Treatment Cycle 3): Changes From Baseline in Daily Average Number of Urinary Incontinence Episodes

  Baseline (Pre-dose of Treatment Cycle 1), Week 0, Week 2, Week 6, Week 12, Week 18 and Week 24 in Treatment Cycle 3

• Treatment Phase 1 (Treatment Cycle 1): Percentage Change From Baseline in 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 100 U

EXPERIMENTAL

Initially, subjects will receive a single (double-blind) treatment with GSK1358820 (20 injections of 0.5 mL each) into the detrusor muscle of the bladder, using cystoscopy, and under local anesthesia. If the criteria for re-treatment are met between 12 and 36 weeks after the first treatment, subjects will receive a second treatment with GSK1358820 (open-label). A third treatment with GSK1358820 (open-label) may be given until 36 weeks after the first treatment, upon meeting the criteria, provided a minimum of 12 weeks elapse since previous treatment. Subjects will receive prophylactic antibiotic therapy beginning up to 3 days prior to treatment and continuing up to 3 days following treatment.

Drug: GSK1358820; Drug: Antibiotic therapy; Other: Bladder diary; Other: King's Health Questionnaire (KHQ); Other: Overactive Bladder Symptom Score (OABSS); Other: Treatment Benefit Scale (TBS)

Placebo Injection

PLACEBO COMPARATOR

Initially, subjects will receive a single (double-blind) treatment with Placebo (20 injections of 0.5 mL each) into the detrusor muscle of the bladder, using cystoscopy, and under local anesthesia. If the criteria for re-treatment are met between 12 and 36 weeks after the first treatment, subjects will receive a second treatment, this time with open-label GSK1358820. A third treatment with open-label GSK1358820 may be given until 36 weeks after the first treatment, upon meeting the criteria, provided a minimum of 12 weeks elapse since previous treatment. Subjects will receive prophylactic antibiotic therapy beginning up to 3 days prior to treatment and continuing up to 3 days following treatment.

Drug: GSK1358820; Drug: Placebo; Drug: Antibiotic therapy; Other: Bladder diary; Other: King's Health Questionnaire (KHQ); Other: Overactive Bladder Symptom Score (OABSS); Other: Treatment Benefit Scale (TBS)

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). 10 mL of the drug will be injected at 20 sites (0.5 mL at each site) in the detrusor muscle, spaced approximately 1 centimeter (cm) apart. The injection will be administered under local anesthesia, via cystoscopy. Permitted anesthesia options for cystoscopy are intraurethral lidocaine (or similar) gel, and for treatment administration, installation of 1-2% lidocaine (or similar anesthetic) into the bladder.

GSK1358820 Injection 100 U; Placebo Injection

Placebo DRUG

Placebo injection is made up of sodium chloride (0.9 mg). 10 mL of the injection will be injected at 20 sites (0.5 mL at each site) in the detrusor muscle, spaced approximately 1 cm apart. The injection will be administered under local anesthesia, via cystoscopy. Permitted anesthesia options for cystoscopy are intraurethral lidocaine (or similar) gel, and for treatment administration, installation of 1-2% lidocaine (or similar anesthetic) into the bladder.

Placebo Injection

Antibiotic therapy DRUG

Subjects will use prophylactic antibiotic therapy approved for the indication of UTIs, at the discretion of the investigator, with the exception of those in the class of aminoglycosides. The therapy will begin 1 to 3 days prior to the administration of study treatment, and continue for 1 to 3 days following the treatment.

GSK1358820 Injection 100 U; Placebo Injection

Bladder diary OTHER

The bladder diary is a self-reporting tool to record subject's data on micturition. Subjects will enter data in the diary over 3 consecutive days. During Screening, data will be collected within 28 days prior to first treatment. During treatment periods, data will be collected within a week prior to each scheduled visit. The bladder diary will capture the following information: 1) Date and time of urinary episode, 2) episodes of micturition, 3) episodes of urinary incontinence, 4) episodes of urgency, 5) intensity of urgency, 6) episodes of nocturia, 7) use of CIC, and 8) urine volume. Diary data will not be collected when a subject experiences symptoms of a UTI.

GSK1358820 Injection 100 U; Placebo Injection

King's Health Questionnaire (KHQ) OTHER

The KHQ will assess the impact of urinary incontinence on QOL. It is a questionnaire with 21 items and the following 9 domains: 1) General health, 2) Incontinence impact, 3) Role limitations, 4) Physical limitations, 5) Social limitations, 6) Personal relationships, 7) Emotion, 8) Sleep/energy, 9) Severity measure. The items are answered by subjects themselves, and scores are summated using a defined algorithm.

GSK1358820 Injection 100 U; Placebo Injection

Overactive Bladder Symptom Score (OABSS) OTHER

The OABSS will comprehensively assess symptoms of OAB, such as frequency of micturition, nocturia, urinary urgency, and urge incontinence. It consists of 4 questions which will be responded by subjects themselves, by selecting the most appropriate answer for each question.

GSK1358820 Injection 100 U; Placebo Injection

Treatment Benefit Scale (TBS) OTHER

The TBS consists of one question ("My condition has"), to which the subject will answer by selecting one of the following responses: greatly improved, improved, not changed, worsened. The TBS will assess treatment benefit of GSK1358820.

GSK1358820 Injection 100 U; 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 symptoms of OAB (frequency and urgency) with urinary incontinence for a period of at least 6 months immediately prior to screening, determined by documented subject history.
• Subject has not been adequately managed with one or more medications (that is, anticholinergics or beta-3 adrenergic receptor agonist) for treatment of their OAB symptom. 'Not adequately managed' is defined as: An inadequate response after at least a 4-week period of OAB medication(s) on an approved optimized dose(s), that is, subject is still incontinent despite medication(s) for OAB; or limiting side effects (that is, condition that subject reduced dosage or discontinued the medication due to side effect after at least a 2-week period of OAB medication(s) on an approved optimized dose(s)).
• Subject who experiences all of the following, in the 3-day subject bladder diary completed during the screening phase:
• \>= 3 episodes of urinary urgency incontinence, with no more than one urgency incontinence-free day
• urinary frequency (defined as an average of \>= 8 micturitions \[toilet voids\] per day, that is, a total of \>= 24 micturitions)
• Subject is willing to use clean intermittent catheterization (CIC) to drain urine if it is determined to be necessary by the investigator (or subinvestigator).
• Body weight \>=40 kilograms (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 the contraceptive options below: 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:
• 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.

You may not qualify if:

• Subject has symptoms of OAB due to any known neurological reason (example, spinal cord injury, multiple sclerosis, cerebrovascular accident, Alzheimer's disease, Parkinson's disease, etc.)
• Subject has a predominance of stress incontinence determined by subject history.
• Subject has a history or evidence of any diseases, functional abnormalities or bladder surgery, other than OAB, 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 prohibited within 7 days prior to the start of the screening phase
• 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 nanograms (ng)/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 history of 2 or more urinary tract infections (UTIs) within 6 months of initiation of Treatment phase 1 (Week 0) or current administration of prophylactic antibiotics to prevent chronic UTIs
• Subject has a positive urine dipstick reagent strip test at initiation of Treatment phase 1 (Week 0) for nitrites or leukocyte esterase, or who are considered by the investigator (or subinvestigator) to have UTI.
• Subject has a serum creatinine level \>2 times the upper limit of normal (ULN) at screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (48)

GSK Investigational Site

Aichi, 466-8560, Japan

Location

GSK Investigational Site

Aichi, 474-8511, Japan

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GSK Investigational Site

Chiba, 264-0017, Japan

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GSK Investigational Site

Chiba, 270-0034, Japan

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GSK Investigational Site

Chiba, 270-1694, Japan

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GSK Investigational Site

Fukui, 910-1193, Japan

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GSK Investigational Site

Fukuoka, 802-8517, Japan

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GSK Investigational Site

Fukuoka, 810-0001, Japan

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GSK Investigational Site

Fukuoka, 814-0022, Japan

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GSK Investigational Site

Fukuoka, 815-8588, Japan

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GSK Investigational Site

Fukuoka, 816-0943, Japan

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GSK Investigational Site

Gifu, 502-8511, Japan

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GSK Investigational Site

Hokkaido, 060-8648, Japan

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GSK Investigational Site

Ibaraki, 309-1793, Japan

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GSK Investigational Site

Ibaraki, 310-0011, Japan

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GSK Investigational Site

Ishikawa, 920-8641, Japan

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GSK Investigational Site

Kagoshima, 890-0073, Japan

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GSK Investigational Site

Kagoshima, 890-8520, Japan

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GSK Investigational Site

Kanagawa, 227-8501, Japan

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GSK Investigational Site

Kanagawa, 231-0861, Japan

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GSK Investigational Site

Kanagawa, 252-0392, Japan

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GSK Investigational Site

Kyoto, 612-8555, Japan

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GSK Investigational Site

Miyagi, 980-0803, Japan

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GSK Investigational Site

Miyagi, 981-0501, Japan

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GSK Investigational Site

Nagasaki, 852-8501, Japan

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GSK Investigational Site

Niigata, 950-8725, Japan

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GSK Investigational Site

Okayama, 700-8558, Japan

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GSK Investigational Site

Okayama, 710-8522, Japan

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GSK Investigational Site

Osaka, 542-0086, Japan

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GSK Investigational Site

Osaka, 554-0012, Japan

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GSK Investigational Site

Osaka, 564-0013, Japan

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GSK Investigational Site

Shiga, 520-2192, Japan

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GSK Investigational Site

Shizuoka, 431-3192, Japan

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GSK Investigational Site

Tochigi, 321-0293, Japan

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GSK Investigational Site

Tokushima, 770-8503, Japan

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GSK Investigational Site

Tokyo, 101-8309, Japan

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GSK Investigational Site

Tokyo, 113-8655, Japan

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GSK Investigational Site

Tokyo, 116-8567, Japan

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GSK Investigational Site

Tokyo, 135-8577, Japan

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GSK Investigational Site

Tokyo, 162-8655, Japan

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GSK Investigational Site

Tokyo, 164-8541, Japan

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GSK Investigational Site

Tokyo, 173-8610, Japan

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GSK Investigational Site

Tokyo, 181-8611, Japan

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GSK Investigational Site

Tottori, 680-0903, Japan

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GSK Investigational Site

Tottori, 683-8504, Japan

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GSK Investigational Site

Toyama, 937-0042, Japan

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GSK Investigational Site

Yamagata, 990-0834, Japan

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GSK Investigational Site

Yamanashi, 409-3898, Japan

Location

Related Publications (2)

• Yokoyama O, Honda M, Yamanishi T, Sekiguchi Y, Fujii K, Nakayama T, Mogi T. OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis). Int J Urol. 2020 Mar;27(3):227-234. doi: 10.1111/iju.14176. Epub 2020 Jan 20.

  PMID: 31957922 BACKGROUND

• Yokoyama O, Honda M, Yamanishi T, Sekiguchi Y, Fujii K, Kinoshita K, Nakayama T, Ueno A, Mogi T. Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial. Int Urol Nephrol. 2021 Nov;53(11):2243-2250. doi: 10.1007/s11255-021-02962-z. Epub 2021 Jul 22.

  PMID: 34292493 DERIVED

MeSH Terms

Conditions

Urinary Bladder, Overactive; Urinary Incontinence

Interventions

Anti-Infective Agents

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

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

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: June 29, 2016
• First Posted: July 1, 2016
• Study Start: August 10, 2016
• Primary Completion: March 6, 2018
• Study Completion: November 12, 2018
• Last Updated: November 27, 2020
• Results First Posted: June 3, 2019

Record last verified: 2020-11

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 (48)