E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME (IC/PBS). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008927 |
E.1.2 | Term | Chronic interstitial cystitis |
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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 |
To assess the efficacy of PD 0299685 in the treatment of symptoms associated with interstitial cystitis/painful bladder syndrome including bladder pain, urinary urgency and frequency.
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of PD 0299685. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria to be eligible for enrollment into the study: Visit 1. The following inclusion criteria have to be met in order for a subject to be randomized into this trial: 1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 2. Male and female subjects aged ≥18 years. 3. Diagnosis of IC/PBS 4. Evidence of cystoscopy within 2 years of screening to confirm the absence of other significant lower urinary tract pathology and the presence or absence of cystoscopic features of IC (eg glomerulations, Hunner’s ulcer). Note: Cystoscopy is mandated within 2 years of enrollment. Subjects who have not had cystoscopy within 2 years of screening may undergo the procedure at screening. However placebo run-in would need to be deferred according to the type of cystoscopy performed (exclusion criterion #8). 5. Moderate to severe IC/PBS at screening (Visit 1) as defined by PUF and ICSI total scores: • PUF total score ≥13 and • ICSI total score ≥7 6. Female subjects must be non-pregnant and non-lactating, and be either, postmenopausal, surgically sterilized, or using an appropriate method of contraception. Women of childbearing potential must have a confirmed negative serum pregnancy test at the Screening visit (Visit 1). See Section 4.4.1 for further details. 7. Subjects who are willing and able to comply with scheduled visits, the self completion of study questionnaires and symptom diaries, and other trial-related activities. Visit 2. The following continuation criteria have to be met in order for subjects to be randomized: 8. Completes at least 4 daily pain scores during the 7 days prior to randomization with a mean daily worst pain severity score of ≥4 (0-10 NRS); the mean severity score is defined as the average of all 24 hr worst pain severity scores recorded in the 7 days prior to randomization. 9. Mean micturition frequency per 24 hours ≥8 as derived from the symptom diary completed prior to Visit 2. |
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E.4 | Principal exclusion criteria |
1. Subjects with symptoms of IC/PBS for less than 6 months prior to Screening. 2. Subjects with a post-void residual (PVR) volume >200 mL at Screening (Visit 1). 3. Subjects with a mean voided volume (MVV) <50 mL or > 350 mL measured over 3 consecutive days as verified by the symptom diary prior to randomization (Visit 2). 4. Subjects with a total volume voided of >3000 mL on average per 24 hours, as verified by the symptom diary completed prior to randomization (Visit 2). 5. Subjects with greater than 1+ hematuria on dipstick test at Screening (Visit 1), unless fully investigated prior to randomization to rule out significant urological disease. • Subjects who are menstruating may be re-screened once menstruation has ceased if they have been found to have hematuria on dipstick testing. 6. Subjects with a microbiologically-proven urinary tract infection at Screening (Visit 1) or randomization (Visit 2). 7. Subjects with the following medical history and co-morbid conditions at Screening (Visit 1): Any history of: Genitourinary tuberculosis, bladder cancer, urethral cancer, prostate cancer; recurrent urinary tract infection (UTI) – defined as 2 or more UTIs over the past 6 months or 3 or more over the last 1 year; lower urinary tract anatomical anomaly eg, clinically significant (grades 3 to 4) urogenital prolapse, urethral and/or bladder obstruction; pelvic radiotherapy. History within prior 3 months of: Bacterial prostatitis; urethritis; active genital herpes. Less than 6 weeks Bacterial cystitis Current history of: Proven genitourinary infection including, but not limited to, vaginitis, or yeast infection; symptomatic urinary tract stone. 8. Subjects who have undergone the following procedures: Any history of: Augmentation cystoplasty, cystectomy or cystolysis, neurectomy Less than 6 months prior to screening: Urogenital surgery such as hysterectomy, urethral sling procedure, urinary incontinence surgery, trans-vaginal surgery, prolapse surgery, vaginal delivery or cesarean section, prostate surgery or treatment, other bladder or urethral surgery which could interfere with bladder function. Less than 3 months prior to screening: Formal therapeutic urethral dilatation or urethrotomy Less than 6 weeks prior to screening: Rigid Cystoscopy, Hydrodistention, laser or electrofulguration of Hunner’s ulcer, prostate biopsy. Less than 2 weeks Flexible Cystoscopy, bladder biopsy, urodynamic (cystometrogram) 9. Subjects with any of the following conditions at Screening (Visit 1): • Indwelling urinary catheters or who perform Intermittent Self Catheterization (ISC); • Passive urinary incontinence (eg, vesicovaginal fistula); • Not capable of independent toileting. 10. Subjects at Screening (Visit 1) who intend to start bladder training program, electrostimulation/neuromodulation therapy (eg, Transcutaneous Electrical Nerve Stimulation (TENS)), acupuncture, or physiotherapy regimen during the study. • Subjects who are on an established regimen for at least 3 months prior to Screening may remain on this as long as it remains unchanged for the duration of the study. 11. Subjects taking the following treatments for their interstitial cystitis at Screening as noted below: Prior 6 months: Any intravesical or transvesical treatment not otherwise specified eg, Botulinum toxin A. Prior 1 month: Intravesical dimethylsulfoxide (DMSO), Intravesical pentosan polysulphate, sodium hyaluronate, heparin, lidocaine or bupivicaine. NOTE: Subjects may remain on ongoing oral medications (with the exception of gabapentin or pregabalin) as background therapy for the treatment of their interstitial cystitis symptoms, provided they have been administered at a stable dose for at least 3 months prior to Screening (Visit 1) and remain unchanged for the duration of the study. Use of gabapentin or pregabalin within 2 weeks of Screening visit (Visit 1). 12. Subjects who have received any investigational drug within 30 days (or 5 times the plasma half life, whichever is longer) preceding the Screening visit, or during the course of the study. 13. History of allergic reaction or significant adverse reaction to gabapentin, pregabalin, or PD 0299685 or hypersensitivity to any ingredients of the formulations. 14. Estimated Glomerular Filtration Rate (eGFRMDRD) ≤60 mL/min estimated from serum creatinine, body weight, age, ethnicity and gender at Screening (Visit 1). 15. Clinically significant abnormal ECG at Screening (Visit 1), including Fridericia’s corrected QT interval (QTcF) >500 msec. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 12 in the worst daily pain severity score as measured by an 11-point Numerical Rating Scale (NRS). Change from baseline to Week 12 in the O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) score. |
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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 | No |
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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | Information not present in EudraCT |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 24 |