Interstitial Cystitis, Bladder Pain Syndrome
Conditions
Keywords
Interstitial cystitis, Bladder pain syndrome, IC/BPS, AQX-1125, SHIP1
Brief summary
The primary objective of this study is to evaluate the effect of 6 weeks of treatment with once daily administration of AQX-1125 compared to placebo on average daily pain in subjects with interstitial cystitis/bladder pain syndrome (IC/BPS), during and after treatment, using a standardized 11-point numerical rating scale (NRS) pain score recorded by electronic diary
Interventions
DRUGAQX-1125
Synthetic SHIP1 activator
DRUGPlacebo
Double blind placebo capsule
Sponsors
Aquinox Pharmaceuticals (Canada) Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Be females, ≥18 and ≤75 years of age, who have consistently had symptoms of bladder pain in addition to urinary urgency and/or urinary frequency for more than 12 months * Have had the diagnosis of interstitial cystitis for \> 6 months (pain for at least 12 months) but ≤15 years * Have average daily pain score of at least 5 out of 10 on the 11-point Numerical Rating Scale \[NRS\] pain scale in the 9 days prior to baseline * Have undergone a cystoscopy and have documented visible signs of bladder bleeding, lesions or glomerulation within the last 36 months prior to baseline. * Subjects if of child bearing potential, must agree to avoid pregnancy and use medically acceptable method of contraception from screening visit and throughout the study. * Must be capable of voiding independently
Exclusion criteria
* Pelvic floor pain (\>5 out of 10 on the 11-point NRS pain scale following a pelvic pain assessment) * Have a body mass index \[BMI\] of \<18 kg/m2 or \>39 kg/m2 * Have had a urinary tract infection including bacterial cystitis within the past 30 days. * Have greater than 1+ hematuria on dipstick test at screening from an unknown cause * History of previous procedure(s) (augmentation cystoplasty, cystectomy, or cystolysis) that has affected bladder function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Daily Bladder Pain Score (e-Diary) | Baseline to Week 6 | Change from baseline to week 6 in the average daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded by e-diary. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary) | Baseline to Week 6 | Change from baseline to week 6 in the maximum daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded by e-diary. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'. |
| Change From Baseline in the Average Bladder Pain Score (Clinic) | Baseline to Week 6 | Change from baseline to week 6 in the average daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded at study visit. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'. |
| Change From Baseline in the Maximum Bladder Pain Score (Clinic) | Baseline to Week 6 | Change from baseline to week 6 in the maximum daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded at study visits. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'. |
| O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline to Week 6 | Change from baseline to week 6 in the O'Leary Sant Symptom and Problem Index combined total scores. Both the ICSI and ICPI consist of 4 questions with responses for the ICSI rated on a scale of 0-5 (maximum score of 20, with a higher score indicating worse symptoms) and for the ICPI on a scale of 0-4 (maximum score of 16, with a higher score indicating worse symptoms). For the combined ICSI/PI the maximum score is 36, with a higher score indicating worse symptoms. |
| Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Baseline to Week 6 | Change from baseline to week 6 in the SF-12v2 questionnaire. Two parameters, PCS (physical component summary) and MCS (mental component summary) were calculated. Both components scores range from 0 to 100 with higher scores indicating better Quality of Life. |
| Voiding Frequency as Recorded by Diary Over a 24 Hour Period | Baseline to Week 6 | For a 24-hour period (within 3 days of the subsequent visit), subjects recorded the frequency of each void prior to visit. The outcome measure was the change from baseline at week 6. |
| Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS] | Baseline to Week 6 | Change in baseline to week 6 in the BPIC-SS participant reported questionnaire total score. The total BPIC-SS score ranges from 0-38, with a higher score indicative of worse symptoms. A score of 19 or more was considered to be discriminating between IC/BPS and overactive bladder at screening. |
Other
| Measure | Time frame | Description |
|---|---|---|
| AQX-1125 Concentrations in Plasma and Urine (Trough Values) | Week 4 and Week 6 | AQX-1125 Plasma and Urine Concentrations were measured at week 4 and week 6. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AQX-1125 1 x AQX-1125 Capsule daily
AQX-1125: Synthetic SHIP1 activator | 37 |
| Placebo 1 x placebo capsule daily
Placebo: Double blind placebo capsule | 32 |
| Total | 69 |
Baseline characteristics
| Characteristic | Total | AQX-1125 | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 8 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 56 Participants | 29 Participants | 27 Participants |
| BMI | 27.5 kg/m^2 STANDARD_DEVIATION 5.31 | 26.2 kg/m^2 STANDARD_DEVIATION 4.71 | 29.1 kg/m^2 STANDARD_DEVIATION 5.62 |
| Duration of Diagnosis | 69.4 Months STANDARD_DEVIATION 55.73 | 63.5 Months STANDARD_DEVIATION 54.43 | 76.3 Months STANDARD_DEVIATION 57.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 37 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 61 Participants | 31 Participants | 30 Participants |
| Region of Enrollment Canada | 44 participants | 24 participants | 20 participants |
| Region of Enrollment United States | 25 participants | 13 participants | 12 participants |
| Sex/Gender, Customized Female | 69 participants | 37 participants | 32 participants |
| Weight | 71.5 kg STANDARD_DEVIATION 14.98 | 67.3 kg STANDARD_DEVIATION 12.4 | 76.5 kg STANDARD_DEVIATION 16.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 37 | 25 / 32 |
| serious Total, serious adverse events | 0 / 37 | 0 / 32 |
Outcome results
Primary
Change From Baseline in the Average Daily Bladder Pain Score (e-Diary)
Change from baseline to week 6 in the average daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded by e-diary. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in the Average Daily Bladder Pain Score (e-Diary) | Baseline | 6.4 units on a scale | Standard Error 0.14 |
| AQX-1125 | Change From Baseline in the Average Daily Bladder Pain Score (e-Diary) | Week 6: Change from Baseline | -2.4 units on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in the Average Daily Bladder Pain Score (e-Diary) | Baseline | 6.7 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in the Average Daily Bladder Pain Score (e-Diary) | Week 6: Change from Baseline | -1.4 units on a scale | Standard Error 0.32 |
Comparison: A sample size of 28 subjects per group had 80% power to detect a 1.5-point difference in the change from baseline pain score between AQX-1125 and placebo assuming a between-subject SD of 2.0 and a 2-sided 5% significance level. Average daily pain scores were calculated using an average of up to the last 7 recordings within 9 days before each visit. Missing data, including premature discontinuation, was imputed using the LOCF approach for the primary efficacy end point of average daily pain scorep-value: 0.06195% CI: [-2.1, 0]ANCOVA
Secondary
Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS]
Change in baseline to week 6 in the BPIC-SS participant reported questionnaire total score. The total BPIC-SS score ranges from 0-38, with a higher score indicative of worse symptoms. A score of 19 or more was considered to be discriminating between IC/BPS and overactive bladder at screening.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS] | Baseline | 29.6 units on a scale | Standard Error 0.59 |
| AQX-1125 | Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS] | Week 6: Change from Baseline | -8.8 units on a scale | Standard Error 1.37 |
| Placebo | Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS] | Baseline | 31.6 units on a scale | Standard Error 0.58 |
| Placebo | Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS] | Week 6: Change from Baseline | -4.0 units on a scale | Standard Error 1.17 |
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.01195% CI: [-9.5, -1.3]ANCOVA
Secondary
Change From Baseline in the Average Bladder Pain Score (Clinic)
Change from baseline to week 6 in the average daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded at study visit. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in the Average Bladder Pain Score (Clinic) | Baseline | 6.7 units on a scale | Standard Error 0.19 |
| AQX-1125 | Change From Baseline in the Average Bladder Pain Score (Clinic) | Week 6: Change from Baseline | -2.6 units on a scale | Standard Error 0.46 |
| Placebo | Change From Baseline in the Average Bladder Pain Score (Clinic) | Baseline | 6.7 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in the Average Bladder Pain Score (Clinic) | Week 6: Change from Baseline | -1.1 units on a scale | Standard Error 0.4 |
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.00895% CI: [-2.8, -0.5]ANCOVA
Secondary
Change From Baseline in the Maximum Bladder Pain Score (Clinic)
Change from baseline to week 6 in the maximum daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded at study visits. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in the Maximum Bladder Pain Score (Clinic) | Baseline | 8.1 units on a scale | Standard Error 0.22 |
| AQX-1125 | Change From Baseline in the Maximum Bladder Pain Score (Clinic) | Week 6: Change from Baseline | -2.8 units on a scale | Standard Error 0.55 |
| Placebo | Change From Baseline in the Maximum Bladder Pain Score (Clinic) | Baseline | 8.0 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in the Maximum Bladder Pain Score (Clinic) | Week 6: Change from Baseline | -1.1 units on a scale | Standard Error 0.5 |
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.02895% CI: [-3, -0.2]ANCOVA
Secondary
Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary)
Change from baseline to week 6 in the maximum daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded by e-diary. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary) | Baseline | 7.6 units on a scale | Standard Error 0.17 |
| AQX-1125 | Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary) | Week 6: Change from Baseline | -2.6 units on a scale | Standard Error 0.42 |
| Placebo | Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary) | Baseline | 7.9 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary) | Week 6: Change from Baseline | -1.4 units on a scale | Standard Error 0.35 |
Comparison: E-diary maximum daily pain scores were calculated using an average of up to the last 7 recordings within 9 days before each visit. Missing data, including premature discontinuation, was imputed using the LOCF approach for the secondary efficacy variable of maximum daily pain scorep-value: 0.0395% CI: [-2.5, -0.1]ANCOVA
Secondary
O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI]
Change from baseline to week 6 in the O'Leary Sant Symptom and Problem Index combined total scores. Both the ICSI and ICPI consist of 4 questions with responses for the ICSI rated on a scale of 0-5 (maximum score of 20, with a higher score indicating worse symptoms) and for the ICPI on a scale of 0-4 (maximum score of 16, with a higher score indicating worse symptoms). For the combined ICSI/PI the maximum score is 36, with a higher score indicating worse symptoms.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline (ICSI/PI) | 27.3 units on a scale | Standard Error 0.83 |
| AQX-1125 | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Week 6: Change from Baseline (ICSI/PI) | -7.3 units on a scale | Standard Error 1.25 |
| AQX-1125 | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline (ICSI) | 14.4 units on a scale | Standard Error 0.48 |
| AQX-1125 | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Week 6: Change from Baseline (ICSI) | -3.8 units on a scale | Standard Error 0.62 |
| AQX-1125 | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline (ICPI) | 12.9 units on a scale | Standard Error 0.39 |
| AQX-1125 | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Week 6: Change from Baseline (ICPI) | -3.6 units on a scale | Standard Error 0.69 |
| Placebo | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline (ICPI) | 14.1 units on a scale | Standard Error 0.34 |
| Placebo | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline (ICSI/PI) | 30.2 units on a scale | Standard Error 0.78 |
| Placebo | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Week 6: Change from Baseline (ICSI) | -1.4 units on a scale | Standard Error 0.57 |
| Placebo | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Week 6: Change from Baseline (ICSI/PI) | -3.0 units on a scale | Standard Error 1.04 |
| Placebo | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Week 6: Change from Baseline (ICPI) | -1.6 units on a scale | Standard Error 0.52 |
| Placebo | O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI] | Baseline (ICSI) | 16.1 units on a scale | Standard Error 0.51 |
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.00795% CI: [-8.8, -1.4]ANCOVA
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.00595% CI: [-4.6, -0.9]ANCOVA
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.01495% CI: [-4.5, -0.5]ANCOVA
Secondary
Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire
Change from baseline to week 6 in the SF-12v2 questionnaire. Two parameters, PCS (physical component summary) and MCS (mental component summary) were calculated. Both components scores range from 0 to 100 with higher scores indicating better Quality of Life.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Baseline (Mental Component) | 46.4 units on a scale | Standard Error 1.34 |
| AQX-1125 | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Week 6: Change from Baseline (Mental Component) | 0.5 units on a scale | Standard Error 1.97 |
| AQX-1125 | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Baseline (Physical Component) | 41.4 units on a scale | Standard Error 1.42 |
| AQX-1125 | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Week 6: Change from Baseline (Physical Component) | 3.8 units on a scale | Standard Error 1.55 |
| Placebo | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Week 6: Change from Baseline (Physical Component) | 1.8 units on a scale | Standard Error 1.22 |
| Placebo | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Baseline (Mental Component) | 41.3 units on a scale | Standard Error 2.2 |
| Placebo | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Baseline (Physical Component) | 36.1 units on a scale | Standard Error 2.11 |
| Placebo | Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire | Week 6: Change from Baseline (Mental Component) | 4.0 units on a scale | Standard Error 1.67 |
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.59295% CI: [-6.3, 3.6]ANCOVA
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.22195% CI: [-1.6, 6.7]ANCOVA
Secondary
Voiding Frequency as Recorded by Diary Over a 24 Hour Period
For a 24-hour period (within 3 days of the subsequent visit), subjects recorded the frequency of each void prior to visit. The outcome measure was the change from baseline at week 6.
Time frame: Baseline to Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Voiding Frequency as Recorded by Diary Over a 24 Hour Period | Baseline | 15.7 number of voids | Standard Error 1.21 |
| AQX-1125 | Voiding Frequency as Recorded by Diary Over a 24 Hour Period | Week 6: Change from Baseline | -3.6 number of voids | Standard Error 1.05 |
| Placebo | Voiding Frequency as Recorded by Diary Over a 24 Hour Period | Baseline | 16.8 number of voids | Standard Error 1.26 |
| Placebo | Voiding Frequency as Recorded by Diary Over a 24 Hour Period | Week 6: Change from Baseline | -0.8 number of voids | Standard Error 0.75 |
Comparison: Analyses of the secondary variable was based on observed data without imputation.p-value: 0.0495% CI: [-5.5, -0.1]ANOVA
Other Pre-specified
AQX-1125 Concentrations in Plasma and Urine (Trough Values)
AQX-1125 Plasma and Urine Concentrations were measured at week 4 and week 6.
Time frame: Week 4 and Week 6
Population: The intent-to-treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | AQX-1125 Concentrations in Plasma and Urine (Trough Values) | Plasma Week 4 | 252 ng/mL | Standard Deviation 129 |
| AQX-1125 | AQX-1125 Concentrations in Plasma and Urine (Trough Values) | Urine Week 6 | 33,396 ng/mL | — |
| AQX-1125 | AQX-1125 Concentrations in Plasma and Urine (Trough Values) | Plasma Week 6 | 225 ng/mL | Standard Deviation 127 |
| AQX-1125 | AQX-1125 Concentrations in Plasma and Urine (Trough Values) | Urine Week 4 | 49,863 ng/mL | — |