Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK1358820 · 7 trials · 5 indications
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.
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.
The strabismus angle in the primary position was measured using the alternative prism cover test (APCT). The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 meters \[m\]) and the near-view strabismus angle (measured at a distance of 33 centimeters \[cm\]). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the value at Week 4 minus the value at Baseline.
A pre-weighed filter paper was placed into the axilla area to collect sweat over a 5-minute period. The paper was removed and weighed to determine the amount of sweat produced. A responder was defined as a participant showing at least a 50% reduction from Baseline in mean weight of axillary sweating.
The investigator, physiotherapist, or occupational therapist extended the participant's wrist as quickly as possible to grade flexor muscle tone. The MAS wrist score was calculated by using the 6-point MAS (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension). Change from Baseline at Week 6 was calculated as the value at Week 6 minus the value at Baseline.
Change from baseline in MAS wrist score using a 6-point scale (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension) to each time point in the DB phase was calculated. In the graph plotting time points on the horizontal axis and changes from baseline on the vertical axis, the area surrounded by the MAS wrist score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS wrist score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.
Change from baseline in MAS ankle score using a 6-point scale (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension) to each time point in the DB phase was calculated. In the graph plotting time points on the horizontal axis and changes from baseline on the vertical axis, the area surrounded by the MAS ankle score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS ankle score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| Non-treatment (10-20 PD) | NO_INTERVENTION | Receive no treatment on Week 0 |
| GSK1358820 1.25 U (10-20 PD) | ACTIVE_COMPARATOR | Receive 1.25 U of GSK1358820 on Week 0 |
| GSK1358820 2.5 U (10-20 PD) | ACTIVE_COMPARATOR | Receive 2.5 U of GSK1358820 on Week 0 |
| Non-treatment (20-50 PD) | NO_INTERVENTION | Receive no treatment on Week 0 |
| GSK1358820 2.5 U (20-50 PD) | ACTIVE_COMPARATOR | Receive 2.5 U of GSK1358820 on Week 0 |
| GSK1358820 5.0 U (20-50 PD) | ACTIVE_COMPARATOR | Receive 5.0 U of GSK1358820 on Week 0 |
| GSK1358820 | ACTIVE_COMPARATOR | Onabotulinum toxin type A |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| GSK1358820(Botulinum Toxin Type A) | EXPERIMENTAL | GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox") |
| High-Dose BTX | ACTIVE_COMPARATOR | - |
| High-Dose Placebo | PLACEBO_COMPARATOR | - |
| Low-Dose BTX | ACTIVE_COMPARATOR | - |
| Low-Dose Placebo | ACTIVE_COMPARATOR | - |
| BTX | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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(Botulinum toxin type A) | DRUG | GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox") |
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 documente...
GSK1358820 is an investigational small molecule being developed for post-stroke spasticity, hyperhidrosis, strabismus, and overactive bladder. It has been studied in patients with upper and lower limb spasticity following a cerebrovascular accident, axillary hyperhidrosis, and strabismus. The drug is in Phase 3 clinical development.
GSK1358820 is a small molecule that targets botulinum toxin type A pathways. It is designed to treat conditions involving muscle overactivity and excessive glandular secretion. The drug's mechanism is being evaluated in clinical trials for post-stroke spasticity, hyperhidrosis, and strabismus.
GSK1358820 is developed by GSK plc, a global biopharma company listed on the London Stock Exchange under the ticker GSK. The company is conducting Phase 3 clinical trials for this investigational drug.
GSK1358820 is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The completed Phase 3 trials studied the drug in post-stroke spasticity, axillary hyperhidrosis, and strabismus.
GSK1358820 has been studied in four completed Phase 3 trials. NCT00460564 and NCT00460655 evaluated the drug in post-stroke upper and lower limb spasticity, respectively. NCT01128738 assessed it in axillary hyperhidrosis, and NCT01584843 examined its efficacy and safety in strabismus.
GSK1358820 is a small molecule that acts on botulinum toxin type A pathways. Clinical trial titles describe it as botulinum toxin A or botulinum toxin type A. It is being studied for conditions typically treated with botulinum toxin injections, such as spasticity and hyperhidrosis.