E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Interstitial Cystitis/Bladder Pain Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Interstitial Cystitis/Bladder Pain Syndrome |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071166 |
E.1.2 | Term | Bladder pain syndrome |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008927 |
E.1.2 | Term | Chronic interstitial cystitis |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the effect of 12 weeks of treatment with 2 different doses of oral AQX-1125 (100 mg or 200 mg) administered once daily compared to placebo on the change from Baseline (Visit 2) to Week 12 (Visit 4) in maximum daily bladder pain in subjects with IC/BPS using a standardized 11-point NRS pain score recorded daily by e-diary. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate:
• The effect of 12 weeks of treatment with 2 different doses of oral AQX-1125 (100 mg or 200 mg) administered once daily compared to placebo on the change from Baseline (Visit 2) to Week 12 (Visit 4) for each of the following:
o Urinary voiding frequency over a 24-hour period.
o ICSI.
o BPIC-SS.
• Overall response to treatment for AQX-1125 100 mg or 200 mg compared to placebo as measured by the subject’s Global Response Assessment (GRA) at Week 12.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in to the screening period subjects must meet the following criteria:
1. Provide written informed consent and the willingness and ability to comply with all aspects of the study requirements.
2. Males/females, ≥18 and ≤80 years of age at Screening Visit 1.
3. Subjects who have consistently had symptoms of bladder pain in addition to urinary urgency and/or urinary frequency for more than 6 months (to ensure a properly established diagnosis).
4. Have had the clinical diagnosis, or history consistent with the diagnosis, of IC/BPS for >3 months but ≤20 years (to ensure a properly established diagnosis).
5. BPIC-SS minimum score as per the study protocol.
6. ICSI minimum score as per the study protocol.
7. Pelvic floor pain maximum score as per the study protocol on the 11-point NRS pain scale following a pelvic pain assessment (to discriminate between bladder pain and perineal/pelvic floor pain masquerading as bladder pain).
8. Must be capable of voiding independently (to allow completion of voiding diary over a 24 hour period).
9. Subjects must fulfil at least one of the following criteria:
• Males/females surgically sterile for a minimum of 6 months; or
o Females: Post-menopausal for a minimum of 1 year; or
o If of child bearing potential, must have a negative pregnancy test and agree to avoid pregnancy and use a highly effective method of contraception with one additional barrier method of contraception from Screening Visit 1 to the final Follow-up Visit of the study (or until at least 28 days after the last dose of study drug has been taken).
o Acceptable methods of highly effective contraception include non-hormonal intrauterine device, intrauterine hormone-releasing system or hormonal contraception (patch, injectable or implantable). Acceptable barrier methods include male condom, diaphragm, cap or sponge, or vasectomy of sole sexual partner.
o If using oral hormonal contraception, the barrier method used must include spermicide.
o True abstinence can be used as a method of contraception, when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception.
o Males: Must use a condom for sexual intercourse from Screening Visit 1 until at least 90 days after last dose of study drug has been taken, unless they have been surgically sterilized (vasectomy).
10. Women of child bearing potential must have a negative pregnancy test at Screening Visit 1, Baseline (Visit 2) and throughout the study.
11. Females are non-lactating (Screening Visit 1, Baseline [Visit 2] and throughout the study).
For inclusion into TP1, subjects must meet the following criteria at Baseline (Visit 2):
12. Have minimum average daily pain score as per the study protocol on the 11-point NRS pain scale (mean of the average daily pain score recorded at each of the 7 days prior to Baseline [Visit 2]).
13. Minimum number of urinary voids as per the study protocol in a 24-hour period recorded within 3 days (72 hours) prior to Baseline (Visit 2).
14. Have undergone a cystoscopy within the last 36 months (inclusive) prior to Baseline (Visit 2). For cystoscopies performed prior to Screening Visit 1, results of that cystoscopy must be available and include presence or absence of Hunner Lesion and additional pathology.
• If the cystoscopy was performed for non-therapeutic purposes, it must have been performed at least 14 days prior to Screening Visit 1.
• If the cystoscopy involved therapeutic hydrodistension, it must have been performed at least 3 months prior to Baseline (Visit 2). The results of that cystoscopy must be available and the information, particularly the presence or absence of Hunner Lesion will be collected; or
• If no cystoscopy has been performed prior to Screening Visit 1, the results are unavailable or do not meet the requirements of the protocol, the subject will have a cystoscopy (without hydrodistension) at Screening Visit 1a, within 14 days of Screening Visit 1 (with Baseline [Visit 2] occurring a minimum of 14 days and a maximum of 28 days after the screening cystoscopy at Screening Visit 1a). |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria at Screening Visit 1 will not be eligible for study participation. However, subjects fulfilling criterion 2 will be eligible for rescreening:
1. Catastrophizing pain score over maximum score allowed per the study protocol as determined by the Pain Catastrophizing Scale (PCS).
2. Have had a urinary tract infection (UTI) including bacterial cystitis within the past 30 days (inclusive) or presence on laboratory C&S at Screening Visit 1. Subjects with current infection may be treated according to standard of care and rescreened at least 10 days after resolution of infection (and have a repeat urine C&S that was documented as clear).
3. Microscopic hematuria that has not been adequately evaluated per local standard of care.
4. History of chronic substance abuse, dependency or abuse of opiates, or other narcotics within the last 2 years.
5. Currently receiving any of the following prohibited medications or procedures:
• Taken antihistamine or NSAID unless on a stable dose for ≥30 days prior to Screening Visit 1.
• Taken any long-acting opiates within 2 weeks prior to Baseline (Visit 2) and throughout the study, or more than 10 short-acting opiates/month. If (short-acting) opiate analgesics are taken during the screening period they should be limited to a maximum of 2 days per week and not within 3 days prior to randomization.
• Oral steroid or cyclosporine therapy within 30 days prior to Screening Visit 1 and throughout the study.
• Had treatment with intravesical therapy within 60 days prior to Screening Visit 1.
• Bladder hydrodistension and/or fulguration within 3 months prior to Screening Visit 1 and throughout the study.
• Have taken any investigational drug within 90 days prior to Screening Visit 1 or have had previous exposure to AQX-1125.
6. History of previous procedure(s) (augmentation cystoplasty, cystectomy, cystolysis, botulinum toxin or bladder catheterization) that has significantly affected bladder function.
7. History of cyclophosphamide or chemical cystitis, urinary tuberculosis or radiation cystitis.
8. Females: History of bladder tumors or uterine, cervical, vaginal or urethral cancer.
9. Males: History of prostate surgery (TURP, TURT, TUIP TUNA etc.), a history of prostate cancer, or currently being treated for chronic bacterial prostatitis.
10. Have any other condition/disease which, in the opinion of the Investigator, could compromise subject safety or interfere with the subject’s participation in the study or in the evaluation of the study results. In case of any doubt, the Investigator shall consult the Medical Monitor.
11. Major surgery within 3 months prior to Screening Visit 1.
12. Known intolerance to micro-crystalline cellulose (Avicel® PH-102), mannitol or other ingredient of AQX-1125 tablets.
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from Baseline (Visit 2) at Week 12 (Visit 4) for AQX-1125 100 mg or 200 mg compared to placebo in the maximum daily bladder pain score based on a standardized 11 point NRS recorded by e-diary as measured by the mean of the maximum scores recorded once daily for a minimum of 5 of the 7 days prior to each visit. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Once daily for a minimum of 5 of the 7 days prior to each of Baseline (Visit 2) , Week 6 (Visit 3) and Week 12 (Visit 4). |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are:
• The change from Baseline (Visit 2) at Week 12 (Visit 4) for AQX-1125 100 mg or 200 mg compared to placebo in the following:
o Voiding frequency measured over a 24-hour period, within a 3 day (72 hours) window before Baseline (Visit 2) and again before Week 12 (Visit 4).
o ICSI.
o BPIC-SS.
• Overall response to treatment for AQX-1125 100 mg or 200 mg compared to placebo as measured by the subject’s GRA at Week 12.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Voiding frequency - measured over a 24-hour period, within a 3 day (72 hours) window before Baseline (Visit 2) and again before Week 12 (Visit 4).
ICSI/BPIC-SS - Baseline (Visit 2), Week 6 (Visit 3) and Week 12 (Visit 4)
GRA - Week 6 (Visit 3) and Week 12 (Visit 4) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Czech Republic |
Denmark |
Germany |
Hungary |
Latvia |
Netherlands |
Poland |
Romania |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LSLV at the end of the 40-week extension period |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |