not applicable

• Register: EUCTR
• Last refreshed on: 31 March 2014
• Main ID: EUCTR2009-018118-21-DE
• Date of registration: 10/05/2010
• Prospective Registration: Yes
• Primary sponsor: Mundipharma Research GmbH & Co. KG
• Public title: not applicable
• Scientific title: An exploratory, randomised, double-blind, placebo-controlled, parallel group, pilot study to assess the analgesic efficacy of oxycodone/naloxone prolonged release tablets (OXN PR) compared to placebo in opioid-naïve Subjects suffering from severe pain due to Bladder Pain Syndrome. - not applicable
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-018118-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Open label phase If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, Germany, Hungary, United Kingdom

Contacts

• Name: Michael Hopp
• Affiliation: Mundipharma Research GmbH & Co. KG

• Name: Michael Hopp
• Affiliation: Mundipharma Research GmbH & Co. KG

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria:
1. Females, 18 years of age or older.
2. Females less than one year post-menopausal must have a negative serum or urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner).
3. Subjects with a history of severe pain due to BPS for at least 6 months (mean average BPS pain over last 6 months = 5, NRS 0 – 10) prior to entry into the study and based on the Investigators’ judgement and clinical experience the Subjects are likely to benefit from WHO step III opioid therapy for the duration of the study.
4. Subjects who experience the complaint of suprapubic pain related to bladder filling, accompanied by all of the following 3 criteria, in the absence of proven urinary infection or other obvious pathology:
• Must have a total score of = 8 on the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and a score of > 0 on each of the 4 questions on the ICSI.
• Must have a total score of = 8 on the O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) and a score of > 0 on each of the 4 questions on the ICPI.
• Must have an average of = 8 voids per day and an average of = 2 voids at night (nocturia) within the last month.
5. Subject’s treatment of pain due to BPS is insufficient (insufficient efficacy or tolerability, based on a clinical judgement).
6. Subjects with a documented history of attempts to optimise the treatment of pain due to BPS.
7. Subject’s pre-study BPS treatment is expected to remain stable throughout the duration of the study (OXN PR or matching placebo are given as add-on therapy).
8. Subjects must not have received opioid containing medication in the last 6 months or ibuprofen (Ibu) during the last 2 weeks on a regular basis (i.e. prescribed medication or more than occasional self medication use for cough, cold etc).
9. Subjects taking pre-study, non-opioid analgesics, and any other concomitant medications, including medications for the treatment of depression and are considered necessary for the Subject’s welfare, and are anticipated to remain stable throughout the Double-blind Phase of the study, and are to be continued under the supervision of the investigator.
10. Subjects willing and able to participate in all aspects of the study and comply with the use of study medication.
Criteria for entry into the Double-blind Phase:
1. Subjects continue to comply with Screening Inclusion/Exclusion criteria.
2. Subjects must have an average of = 8 voids per day and an average of = 2 voids (nocturia) at night as assessed in a diary recording 2 periods of 24 hours during the Screening Period.
3. Subjects must not have any indication for current acute bacterial cystitis based on urinalysis (urine dipstick) assessed at Visit 2.
4. Subjects with a mean pain value of = 5 (average pain value over the last 24 hours) as assessed during the last 7 days prior to Visit 2.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years
Exclusion criteria:
Exclusion criteria:
1. Females who are pregnant (positive ß-hCG test) or lactating.
2. Subjects with any contraindication/history of hypersensitivity to oxycodone, naloxone, ibuprofen (Ibu), related products or other ingredients.
3. Subjects who previously received ibuprofen regularly for treatment of BPS pain without demonstrating any relevant analgesic effect.
4. Subjects with a history of, or existing peptic ulceration that would place the Subject at risk upon exposure to ibuprofen or that may confound the analysis and/or interpretation of the study results.
5. Subjects with a history of bronchospasm, rhinitis, urticaria, particularly associated with therapy with aspirin or other non-sterioidal anti-inflammatory drugs (NSAIDs).
6. Subjects with any situation in which opioids are contraindicated like severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma or paralytic ileus.
7. Subjects with myxoedema, untreated hypothyroidism, Addison`s disease or increase of intracranial pressure.
8. Subjects with uncontrolled seizures or convulsive disorder.
9. Evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal (e.g. paralytic ileus), or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination, that would place the Subject at risk upon exposure to the study medication or that may confound the analysis and/or interpretation of the study results.
10. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (> 3 times the upper limit of normal), gamma glutamyl transpeptidase (GGT or GGTP) > 3 times the upper limit of normal.
11. Abnormal total bilirubin and/or creatinine level(s) (> 1.5 times the upper limit of normal).
12. Active alcohol or drug abuse and/or history of opioid abuse.
13. Subjects with a positive urine drug test at screening Visit 1, which indicates unreported illicit drug use or unreported use of a concomitant medication not required to treat the Subjects’ medical condition(s).
14. Subjects suffering from documented confusable diseases for bladder pain syndrome (see Appendix 12.5) determined by the medical history/physical examination, urine dip stick test or if needed ultrasound.
15. Chronic or intermittent pain that results from pain conditions other than Bladder Pain Syndrome (BPS) requiring opioid analgesics.
16. Subjects who received a botulinum toxin injection in the bladder wall within the last 6 months prior to the Screening Visit.
17. Subjects who received a hydrodistension within the last 4 months prior to the Screening Visit.
18. Subjects who have had cystoscopic evaluation within 4 weeks prior to the Screening Visit.
19. Subjects presently taking, or who have taken, naloxone = 30 days prior to the Screening Visit.
20. Subjects presently taking or who have taken monoamine oxidase inhibitors (MAOI) = 2 weeks prior to the Screening Visit.
21. Subjects receiving hypnotics or other central nervous system (CNS) depressants that, in the investigator’s opinion, may pose a risk of additional CNS depression with opioid study medication.
22. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days prior to the Screening Visit.
23. Surgery within 2 months prior to the Screening Visit, or planned surgery

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Bladder Pain Syndrome (BPS), formerly addressed as IC/PBS (interstitial cystitis /Painful Bladder Syndrome)
MedDRA version: 14.1 Level: LLT Classification code 10008927 Term: Chronic interstitial cystitis System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

Intervention(s)

Trade Name: Targinact 5mg/2.5 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 5/2.5 mg
Product Code: OXN 5/2.5 mg PR
Pharmaceutical Form: Prolonged-release tablet
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5.0-
CAS Number: 357-08-4
Other descriptive name: NALOXONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: Targinact 10 mg/5 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 10/5 mg
Product Code: OXN 10/5 mg PR
Pharmaceutical Form: Prolonged-release tablet
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10.0-
CAS Number: 357-08-4
Other descriptive name: NALOXONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5.0-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: Targinact 20mg/10 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 20/10 mg
Product Code: OXN 20/10 mg PR
Pharmaceutical Form: Prolonged-release tablet
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20.0-
CAS Number: 357-08-4
Other descriptive name: NALOXONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10.0-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: Targinact 5mg/2.5 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release t

Primary Outcome(s)

Primary end point(s): The Efficacy Variable of main interest is the Pain Intensity Scale – Average pain over the last 24 hours, as assessed at each study Visit during the Double-blind phase

Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned

Main Objective: The aim of this study is to investigate the efficacy and safety of OXN PR in the treatment of BPS and to further support the evidence for the use of opioids in this indication. The main objective is to estimate the Subjects’ average pain over the last 24 Hours assessed at each study Visit during treatment with OXN PR compared with placebo as measured by the Pain Intensity Scale (NRS 0 – 10).

Secondary Objective: - To assess the frequency of pain rescue medication intake.
- To assess BPI-SF at each clinic Visit during treatment with study medication.
- To assess the efficacy based on the O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) score/ O’Leary-Sant Interstitial Cystitis Problem Index (ICPI) score.
- To assess overall health based on the SF-36 v2.
- To assess micturition (volume and time) based on 24 hours patient diary assessing 2 days in the last week prior to Visits 6, 8, 10 and 16.
- To assess urinary urgency using the Patients' Perception of Intensity of Urgency Scale (PPIUS).

Secondary Outcome(s)

Secondary end point(s): - Frequency of analgesic rescue medication use.
- The ICSI and the ICPI measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis (IC). Psychometric performance of both instruments is good, with the ICSI demonstrating excellent ability to discriminate characteristics between patients and controls. Both indices have been useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important. The ICSI contains 4 items that measure urgency and frequency of urination, night-time urination, and pain or burning. The ICSI index score is the sum of the item scores (range: 0 – 20) and it is a valid, reliable, and responsive measure of change in IC symptoms.
- Pain severity subscale score and interference of pain subscale score from the Brief Pain Inventory- Short Form (modified BPI-SF). The Pain severity subscale score is the mean of the (non-missing scores from the) 4 pain intensity items and the Interference subscale score is the mean of the (non-missing scores from the) 7 interference items. Further detail on the computation of these subscale scores will be specified in the statistical analysis plan.
- The SF-36 v2 health survey. The summary scores to be employed are the SF-36 v2 scores for the 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, the health transition question, and 2 summary measures of physical health (aggregate of physical functioning, role-physical, bodily pain and general health scales) and mental health (aggregate of the vitality, social functioning, role-emotional and mental health scales). The scoring algorithms for the subscale scores are described in the statistical analysis plan.
- Micturition diary (volume and time).PPIUS. The PPIUS is a validated, 5-point scale designed to assess patient perception of intensity of urgency. The scale ranges from 0 to 4 with grades 3 and 4 representing urgency and urgency incontinence.
- Pain Intensity Scale – Average pain over the last 24 hours, as assessed at each study Visit during the Open-label Phase.

Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned

Secondary ID(s)

OXN2503

Source(s) of Monetary Support

Mundipharma Research GmbH & Co. KG