Clinical trial NCT00261495: A Study of the Effectiveness and Safety of Sustained-release Hydromorphone (a Strong Opioid) in Patients With Chronic Noncancer Pain.
Official title: Randomized, Open-Label, Comparative Parallel Group Study to Assess Efficacy and Safety on Flexible Dosages of OROS Hydromorphone Once-Daily Compared to Sustained Release Oxycodone Twice Daily in Subjects With Chronic Non-malignant Pain Requiring Continuous Opioid Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Keywords: chronic noncancer pain
pain
analgesia
analgesic opioid
oxycodone
hydromorphone
Lead sponsor: Janssen Pharmaceutica N.V., Belgium
Sponsor class: INDUSTRY
First posted: 2005-12-05
Enrollment: 504
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effectiveness and safety of sustained- release hydromorphone, formulated to release slowly over time, taken once daily, and controlled- release oxycodone taken twice daily, in patients with chronic non-cancer pain. The study will also determine the dose of sustained-release hydromorphone that provides a level of pain control that is equal to the pain control provided by control-released oxycodone (equi-analgesic dosage).

Detailed description: Conventional immediate-release forms of hydromorphone and oxycodone have a relatively short duration of action that require dosing every 4 to 6 hours. To counterbalance the drawback of repeated opioid intake, sustained-release formulations of oxycodone and hydromorphone were developed that allow twice-daily dosing. Subsequently, a novel, once-daily, extended-release hydromorphone formulation was developed to further enhance ease of treatment and improve effectiveness in the treatment of severe pain. This is a randomized, open-label, comparative, parallel-group, 24-week flexible-dose study in patients with chronic noncancer pain severe enough to require continuous opioid therapy. Patients will receive either 8 mg of sustained-release hydromorphone, taken once daily or 10 mg of controlled-release oxycodone, taken twice daily. Individual adjustments in dosing will be performed to achieve satisfactory pain control, up to a maximum daily dosage of 32 mg for hydromorphone and 80 mg for oxycodone. The primary efficacy outcome will be the determination of the dose of hydromorphone that produces a level of pain control that is equal to the pain control provided by oxycodone (equi-analgesic dose). Safety will be monitored throughout the study. The study hypothesis is that sustained-release hydromorphone taken once daily is well tolerated and is not inferior with regard to pain control to controlled-release oxycodone taken twice daily.

Amendment:

Amendment was made to the duration of the study from duration of '24 weeks' to '52 weeks' in order to collect long-term safety and efficacy data. OROS hydromorphone 8, 16, or 32 mg tablets QD or SR oxycodone 10, 20, or 40 mg tablets BID. Individual adjustments in dosing performed to achieve satisfactory pain control over 24 weeks. Amendment: treatment duration was extended to 52 weeks.

Eligibility criteria: Inclusion Criteria:

* Adult patients with chronic noncancer pain severe enough to require continuous opioid therapy (a score of at least 5 in "pain right now" on a 11 point numeric rating scale) who have never received an opioid or are currently treated with a weak opioid, and who experience insufficient pain control.

Exclusion Criteria:

* Patients who have been treated with strong opioids (including hydromorphone and oxycodone) within the last 4 weeks prior to study inclusion or who will probably undergo any treatment (e.g. neurological techniques, surgery) within the next 6 months, which may abruptly alter degree or nature of pain experienced
* patients with a history of disease(s), current illness, or therapy which would preclude them from participation in the study
* and patients who are pregnant or nursing.

Primary outcomes:
measure: Change From Baseline in Brief Pain Inventory (BPI) Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Per Protocol [PP] Population)
timeFrame: baseline and week 24
measure: Change From Baseline in BPI Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Intent to Treat [ITT] Population)
timeFrame: baseline and week 24
measure: Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (PP Population)
timeFrame: week 24
measure: Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (ITT Population)
timeFrame: week 24
measure: Equi-analgesic Dose at Steady-state (PP Population)
timeFrame: week 4 to week 24
measure: Equi-analgesic Dose at Steady State (ITT Population)
timeFrame: week 4 to week 24
Secondary outcomes:
measure: Change From Baseline in BPI Pain Severity Sub-score "Pain at Its Worst" (BPI Item 3) at Week 24 (ITT Population)
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Subject Diary Evening Mean Pain Score "Pain Right Now" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Subject Diary Morning Mean Pain Score "Pain Right Now" at Week 24
timeFrame: baseline and week 24
measure: Number of Subjects With Dose Escalation
timeFrame: week 4 and week 24
measure: Change From Baseline in BPI Severity Score "Pain Right Now" (BPI Item 6) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in BPI Pain Severity Score "Pain at Its Least" (BPI Item 4) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in BPI Pain Severity "Pain at Its Worst" (BPI Item 3) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in BPI Pain Severity "Pain at Its Least" (BPI Item 4) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in BPI Interference Score "Interfered With General Activity" (BPI Item 9a) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With Mood" (BPI Item 9b) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With Normal Work" (BPI Item 9d) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With Sleep" (BPI Item 9f) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Pain Interference "Pain Interfered With General Activity" (BPI Item 9a) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Pain Interference "Pain Interfered With Mood" (BPI Item 9b) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Pain Interference "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Pain Interference "Pain Interfered With Normal Work" (BPI Item 9d) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Pain Interference "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Pain Interference "Pain Interfered With Sleep" (BPI Item 9f) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Pain Interference "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in BPI Pain Severity, Relief and Interference Scores (Extension Phase)
timeFrame: baseline and week 52
measure: Change From Baseline in Sleep Quality (MOS Index I) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Sleep Quality (MOS Index II) at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in Sleep Quality (MOS Index II) at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality, Sleep Disturbance at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality, Snoring at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality, Sleep Shortness of Breath or Headache at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality, Sleep Adequacy at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality, Sleep Somnolence at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality, Sleep Quantity at Week 24
timeFrame: baseline and week 24
measure: Number of Subjects Indicating That They Had Optimal Sleep at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Sleep Quality at Week 52
timeFrame: baseline and week 52
measure: Number of Subjects Indicating Optimal Sleep at Week 52
timeFrame: week 52
measure: Change From Baseline in Subject Diary Mean Pain Evening, Morning, and All Day Scores at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in Subject Diary Mean Pain Score for "Pain at Its Worst" From Morning to Evening at Weeks 4, 8, 12, 16, 20, and 24
timeFrame: baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Number of Subjects With Dose Escalation at Week 4 (ITT Population)
timeFrame: week 4
measure: Number of Subjects With Dose Escalation at Week 24 (ITT Population)
timeFrame: week 24
measure: Change From Baseline in Quality of Life (QoL) "Bodily Pain" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "General Health Perceptions" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Health Transition" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Mental Health" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Physical Functioning" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Role Emotional" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Role Physical" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Social Functioning" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Vitality" at Week 4
timeFrame: baseline and week 4
measure: Change From Baseline in QoL "Bodily Pain" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "General Health Perceptions" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Health Transition" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Mental Health" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Physical Functioning" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Role Emotional" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Role Physical" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Social Functioning" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL "Vitality" at Week 24
timeFrame: baseline and week 24
measure: Change From Baseline in QoL at Week 52
timeFrame: baseline and week 52
measure: Clinical Global Assessment of Efficacy
timeFrame: weeks 4, 24, and 52
measure: Change in Dose of Study Treatment
timeFrame: weeks 4, 24, and 52
measure: Change in Dose of Study Treatment During Titration Phase (First 4 Weeks of Study) and Overall Treatment Phase I (First 24 Weeks of Study)
timeFrame: weeks 4 and 24
measure: Number of Drop-outs
timeFrame: baseline to week 24 (core); week 24 to week 52 (extension)
measure: Number of Days With add-on Pain Medication
timeFrame: week 24
measure: Amount of add-on Pain Medication
timeFrame: 24 weeks
measure: Mode and Convenience of Drug Intake.
timeFrame: weeks 4, 24, and 52
measure: Resource Utilization of Pain Management
timeFrame: week 24
Other outcomes:
Locations:
city: Brno
country: Czech Republic
city: Plzen
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Praha 8
country: Czech Republic
city: Esbjerg N/A
country: Denmark
city: København
country: Denmark
city: Nyborg N/A
country: Denmark
city: Svendborg N/A
country: Denmark
city: Vejle
country: Denmark
city: Amiens Cedex 1
country: France
city: Bois Guillaume
country: France
city: Lille
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Drensteinfurt
country: Germany
city: Dresden
country: Germany
city: Duderstadt
country: Germany
city: Frankfurt
country: Germany
city: Giessen
country: Germany
city: Göppingen
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Jena
country: Germany
city: Kiel
country: Germany
city: Kÿln
country: Germany
city: Ludwigshafen
country: Germany
city: Mannheim
country: Germany
city: Nürnberg
country: Germany
city: Regensburg
country: Germany
city: Rodgau
country: Germany
city: Wiesbaden
country: Germany
city: Bodø
country: Norway
city: Lørenskog
country: Norway
city: Oslo N/A
country: Norway
city: Oslo
country: Norway
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Martin
country: Slovakia
city: Prešov
country: Slovakia
city: Ljubljana
country: Slovenia
city: Maribor
country: Slovenia
city: Slovenj Gradec
country: Slovenia
city: Göteborg
country: Sweden
city: Jönköping
country: Sweden
city: Kristianstad
country: Sweden
city: Linköping
country: Sweden
city: Aarau
country: Switzerland
city: Basel
country: Switzerland
city: Lausanne
country: Switzerland
Study officials:
affiliation: Janssen Pharmaceutica N.V.
name: Janssen Pharmaceutica N.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Binsfeld H, Szczepanski L, Waechter S, Richarz U, Sabatowski R. A randomized study to demonstrate noninferiority of once-daily OROS((R)) hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain. Pain Pract. 2010 Sep-Oct;10(5):404-15. doi: 10.1111/j.1533-2500.2009.00342.x.