E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME. |
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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 |
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. Subjects undergoing general anesthetic cystoscopy may be included at the discretion of the Pfizer study clinician, and any such case should be discussed prior to their enrollment. 5. Moderate to severe IC/PBS at screening (Visit 1) as defined by PUF and ICSI total scores: • PUF total score ≥13 with a score of 2 or greater on question 5 (pain) • 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 5.4 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. Symptoms of IC ≤6 months prior to Screening 2. Post-void residual volume >200 mL at Screening 3. Mean voided volume <50 mL or > 350 mL 4. Total volume voided >3000 mL per 24 hours 5. Greater than 1+ hematuria on dipstick at Screening, unless fully investigated prior to randomization. Subjects who are menstruating may be re-screened once menstruation has ceased 6. Proven UTI at Screening or randomization 7. Medical history at Screening •Any history of: Genitourinary tuberculosis, high grade/stage bladder cancer of any histological type, urethral cancer, prostate cancer; recurrent urinary tract infection defined as ≥ 2 UTIs in past 6 months or ≥ 3 in 1 year; lower urinary tract anatomical anomaly, urethral and/or bladder obstruction; pelvic radiotherapy. •≤5 years Low grade/stage TCC •History within prior 3 months of: Bacterial prostatitis; urethritis; active genital herpes. •≤ 6 weeks Bacterial cystitis •Current history of: Proven genitourinary infection, symptomatic urinary tract stone. 8. Subjects who have undergone the following procedures: •Any history of: Augmentation cystoplasty, cystectomy or cystolysis, neurectomy •≤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. •≤3 months prior to screening: Formal therapeutic urethral dilatation or urethrotomy •≤6 weeks prior to screening: Cystoscopy under general anesthetic, Hydrodistention, laser or electrofulguration of Hunner’s ulcer, prostate biopsy. •≤2 weeks Cystoscopy under local anesthetic, bladder biopsy, urodynamics (cystometrogram) 9. The following conditions at Screening: Indwelling urinary catheters or who perform Intermittent Self Catheterization, Passive urinary incontinence, Incapable of independent toileting 10. Subjects at Screening who intend to start bladder training program, electrostimulation/neuromodulation, acupuncture, or physiotherapy during the study Subjects who are on an established regimen for ≥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: Intravesical Botulinum toxin A or BCG •Prior 3 months: Biologic agents •Prior 1 month: Other intravesical treatments not otherwise specified, including butnot limited to dimethylsulfoxide, pentosan polysulphate, sodium hyaluronate,heparin, chondroitin sulfate, lidocaine or bupivicaine. •Prior 2 weeks: Oral gabapentin or pregabalin 12. Receipt of 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. Subjects who have received tanezumab in a previous study should wait at least 147 days from dosing until randomization in this study 13. History of allergic or hypersensitivity reaction to gabapentin, pregabalin, or PD 0299685 or ingredients of the formulations 14. Estimated Glomerular Filtration Rate (eGFR by Cockcroft-Gault) ≤60 mL/min at Screening 15. Clinically significant abnormal ECG at Screening including QTcF >500 msec 16. Clinically significant abnormalities on Screening laboratory tests 17. Suicide Behaviors Questionnaire – Revised score ≥8 at screening 18. Patient Health Questionnaire – 9 total score ≥15 or a score ≥1 on question 9 19. Subjects who answer “yes” on either question 1 or 2 of the Suicide Ideation section or “yes” to any of the 6 questions in the Suicidal Behavior section of the Columbia-Suicide Severity Rating Scale at Screening or Randomization, otherwise determined a significant current risk for suicidal or violent behavior 20. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder associated with hospital admission or suicide attempt within the last 5 years 21. Subjects who intend to donate blood during the study or within 30 days after last scheduled study visit 22. History of malignancy within the past 2 years except basal cell carcinoma curatively treated 23. Drugs of abuse on urine drug screen, unless arising from medication that is medically indicated or prescribed by a physician 24. Alcohol or drug abuse within the past 2 years 25. Significant, uncontrolled acute or chronic disease which would increase the risk associated with study participation or would make the patient inappropriate for entry into this study |
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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
| Yes |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |