Last updated: 07/13/2021 12:10:05
Efficacy and safety study of GSK1358820 in Japanese patients with urinary incontinence due to neurogenic detrusor overactivity
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A phase III study to evaluate the efficacy and safety of GSK1358820 (botulinum toxin type A) in patients with urinary incontinence due to neurogenic detrusor overactivity
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from baseline in the daily average number of urinary incontinence episodes at Week 6 after the first treatment
Timeframe: Baseline and at Week 6
Secondary outcomes:
Change from baseline in maximum cystometric capacity (MCC) at Week 6 after the first treatment
Timeframe: Baseline and at Week 6
Change from baseline in maximum detrusor pressure during the first involuntary detrusor contraction (IDC)（PmaxIDC) at Week 6 after the first treatment
Timeframe: Baseline and at Week 6
Change from baseline measured by volume at first IDC (VPmaxIDC) at Week 6 after the first treatment
Timeframe: Baseline and at Week 6
Change from baseline measured by maximum detrusor pressure during the storage phase (PdetMax) at Week 6 after the first treatment
Timeframe: Baseline and at Week 6
Change from baseline in daily average number of urinary incontinence episodes
Timeframe: Baseline and up to Week 48
Percentage change from baseline in daily average number of urinary incontinence episodes
Timeframe: Baseline and up to Week 48
Change from baseline in daily average number of voids
Timeframe: Baseline and up to Week 48
Percentage change from baseline in daily average number of voids
Timeframe: Baseline and up to Week 48
Change from baseline in average volume voided per micturition
Timeframe: Baseline and up to Week 48
Percentage change from baseline in average volume voided per micturition
Timeframe: Baseline and up to Week 48
Percentage of subjects attaining pre-specified target reduction from baseline in the daily average of urinary incontinence episodes
Timeframe: Baseline and up to Week 48
Duration of treatment effect after first treatment measured by time to qualification for retreatment after first treatment
Timeframe: Week 12 to Week 36
Duration of treatment effect after first treatment measured by ‘time to request for retreatment after first treatment’
Timeframe: Week 12 to Week 36
Changes from baseline in King’s Health Questionnaire (KHQ) domain score
Timeframe: Baseline and up to Week 48
Percentage of subjects with positive response on the Treatment Benefit Scale (TBS)
Timeframe: Week 2 to Week 48
Interventions:
Drug: GSK1358820
Drug: Placebo
Enrollment:
21
Observational study model:
Not applicable
Primary completion date:
2018-02-03
Time perspective:
Not applicable
Clinical publications:
Masashi Honda, Osamu Yokoyama, Ryosuke Takahashi, Tatsuma Matsuda, Takashi Nakayama, Takao Mogi. 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;
DOI: 10.1111/iju.14602
PMID: 34075630
Medical condition
Urinary Bladder, Overactive
Product
OnabotulinumtoxinA
Collaborators
Not applicable
Study date(s)
October 2016 to December 2018
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
20+ years
Accepts healthy volunteers
No
- 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:
- 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
Inclusion and exclusion 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
- 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).
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:
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.
Trial location(s)
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2018-02-03
Actual study completion date
2018-20-12
Plain language summaries
Summary of results in plain language
Available language(s): English, Japanese
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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