Trial document




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  DRKS00000577

Trial Description

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Title

Randomised double-blind, cross-over Phase III study to investigate the efficacy and safety of oxycodone after once daily administration of Oxycodone HCl XL tablets in comparison to twice daily administration of Oxygesic tablets in patients with chronic pain

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This clinical trial is conducted to investigate whether once daily administration of Oxycodone HCl XL tablets - a new prolonged formulation of oxycodone hydrochloride - is as least as effective (or even more effective) as twice daily administration of Oxygesic tablets - a marketed formulation of oxycodone hydrochloride (brand name Oxygesic in Germany) - at the same daily dosage.

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Brief Summary in Scientific Language

The use of Oxycodone for control of moderate to severe pain to reach stable analgesia is current standard treatment. Currently, oxycodone hydrochloride controlled release preparations for twice daily application are marketed in the European Union, e.g. Oxygesic in Germany by Mundipharma. Oxycodone HCL XL the product under clinical investigation, is a new formulation that is thought to be as effective as Oxygesic but only needs to be taken once daily. It is intended for the management of moderate-to-severe pain in patients requiring continuous analgesic treatment and it is expected that the once daily administration will contribute to improve compliance and pain control.
Objective of the prospective, multicentre, randomised, double-blind, active-controlled, adaptive, two-treatment, two-period, two-sequence, crossover study in patients with chronic cancer pain is to demonstrate that at the same daily dosage once daily administration of Oxycodone HCl XL tablets is at least as effective as twice daily administration of Oxygesic tablets.
The titration period is to adjust the study participants to adequate dose of Oxygesic. When adequate and stable analgesia is attained, the patients will be randomised to double-blind treatment with the study medication. Two 10-day double-blind treatment periods will follow at this stable total daily dose (TDD). During titration and both treatment periods data will be recorded and assessed for pain intensity (VAS on defined time points), overall effectiveness (CAT), use of rescue medication and adverse events. Patients will use daily diaries for self-assessment. In a subset of maximum 20 patients concentrations of oxycodone will be determined in plasma separated from venous blood samples collected during both treatment periods.
After 36 randomised and completed patients, an unblinded interim analysis will be conducted in order to adapt the sample size and make further decisions on stopping the study due to early success or no success or to continue the study with an adapted sample size.

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Organizational Data

  •   DRKS00000577
  •   2010/10/29
  •   [---]*
  •   no
  •   Approved
  •   2010-244-f-A, Ethik-Kommission der Ärztekammer Westfalen-Lippe und der med. Fakultät der Westfälischen Wilhelms-Universität Münster
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Secondary IDs

  •   2010-020402-15 
  •   4036460 
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Health Condition or Problem studied

  •   chronic cancer pain
  •   R52.2 -  Other chronic pain
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Interventions/Observational Groups

  •   once daily administration of Test Product Oxycodone HCl XL (and additionally Placebo for blinding as the Reference Product is given twice daily)
  •   twice daily administration of the Reference Product Oxygesic
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Crossover
  •   III
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Primary Outcome

to demonstrate that once daily administration of Oxycodone HCl XL tablets is at least as effective as twice daily administration of Oxygesic tablets at the same daily dosage.
The primary efficacy endpoint is defined as overall "current" pain intensity (PI) on 0 - 100 mm VAS (mean "current" PI of the last 5 days of each treatment period). Pain intensity on 0 - 100 mm VAS at predefined time points will be collected through patient diaries. Mean "current" PI of the last 5 days of each tratment period will be analysed by means of an analysis of variance (ANOVA)). Non-inferiority of Oxycodone HCl XL tablets for once daily dosing will be concluded if the upper limit of the two-sided 95% confidence interval of the treatment difference between the test product and Oxygesic tablets does not exceed 12 mm in the overall "current" pain intensity (PI) on 0 - 100 mm VAS (mean "current" PI of the last 5 days of each treatment period).

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Secondary Outcome

- In the case of non-inferiority, to demonstarte that once daily administration of Oxycodone HCl XL tablets is more effective (superior) as twice daily administration of Oxygesic tablets at the same daily dosage
- to assess the safety and tolerability of once daily administration of Oxycodone HCl XL tablets in comparison with twice daily administration of Oxygesic tablets
- to investigate the oxycodone plasma concentrations during treatment with once daily administration of Oxycodone HCl XL tablets in comparison with twice daily administration of Oxygesic tablets (in a subset of maximum 20 patients)

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Countries of Recruitment

  •   Germany
  •   Poland
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Locations of Recruitment

  • [---]*
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Recruitment

  •   Actual
  •   2011/03/03
  •   60
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. Caucasian male and female patients >18 years of age with chronic cancer or non-cancer pain.
2. Patients with predominantly non-neuropathic pain (assessed by e.g. the DN4 Neuropathic Pain Diagnostic Questionaire).
3. Patients requiring continuous oral opioid therapy with at least 40 mg oxycodone per day (or equivalent).
4. Adequate analgesia (mean "current" pain intensity per day ≤40 mm on VAS) prior to randomisation for at least three consecutive days.
5. Stable analgesic requirements prior to randomisation for at least three days (stable maintenance dose of oxycodone; requirement of at least 40 mg mg oxycodone per day; ≤2 doses of rescue medication per day), tolerable AEs).
6. ECOG (Eastern Cooperative Oncology Group) performance status <3.
7. Life expectancy of at least 3 months
8. Female patients of childbearing potential agree to undergo pregnancy tests.
9. Willingness to undergo a pre-study physical examination and pre- and post-study laboratory investigations.
10. Ability to comprehend and willingness to sign informed consent.

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Exclusion Criteria

1.Hypersensitivity to oxycodone or any of the excipients of the study drugs.
2.Patients requiring more than 120 mg oxycodone per day (or equivalent).
3.Surgery within 1 month prior to study start and/or anticipated or scheduled surgical intervention during the study.
4.Intravenous chemotherapy and/or radiotherapy for pain alleviation and/or neural blockade within 2 weeks prior to study start and/or anticipated and/or scheduled during the course of the study.
5.Known or suspected clinically significant respiratory depression, hypoxia, hypercapnia, or decrease in respiratory reserve.
6.Known or suspected severe obstructive pulmonary disease, acute or severe bronchial asthma, or cor pulmonale.
7.Known or suspected significant hepatic impairment (hepatic transaminases >3 times the upper limit of normal).
8.Known or suspected severe renal impairment (CRCL <30 ml/min) or patients with renal failure who are on any form of dialysis.
9.Known or suspected significant circulatory disturbance, hypotension, or circulatory shock.
10.Known or suspected clinically relevant endocrine disorder, such as myxoedema, not adequately treated hypothyroidism or adrenocortical insufficiency (e.g. Addison's disease)
11.Known or suspected paralytic ileus, significant impairment of bowel motility severe enough to potentially result in ileus.
12.Known or suspected acute or chronic pancreatitis or biliary tract disease.
13.Any gastro-intestinal pathology or surgery or intractable vomiting likely to significantly influence drug absorption.
14.Inability to swallow the study drugs whole (e.g. due to dysphagia).
15.Known or suspected significant prostatic hypertrophy or urethral stricture severe enough to potentially result in urinary retention.
16.Known or suspected CNS depression (signs/symptoms: decreased vital signs, impaired thinking and perception, slurred speech, slowed reflexes, fatigue, decreased consciousness), coma, or convulsive disorder.
17.Known or suspected elevation of intracranial pressure.
18.Known or suspected acute alcoholism, delirium tremens, or toxic psychosis.
19.History of drug addiction or drug seeking behaviour.
20.Concomitant treatment with MAO inhibitors.
21.Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to practice adequate contraceptive measures. Reliable methods for women are orally administered hormonal contraceptives, surgical intervention (e.g. tubal ligation), intrauterine device (IUD) and sexual abstinence.
22.Any other condition of the patient that in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient’s compliance or adherence to protocol requirements.
23.Previous enrolment in this study or participation in any other drug investigational trial within the past 30 days (or five half-lives whichever is longer) prior to enrolment.
24.Persons suspected to be at risk of suicide.
25.Persons who are not suitable for inclusion in the study in the opinion of the investigator.

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Addresses

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    • Develco Pharma Schweiz AG
    • Hauptstrasse 67
    • CH-4102  Binningen
    • Switzerland
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    • Develco Pharma Schweiz AG
    • Ms.  Dr.  Martina  Maritz 
    • Hauptstr. 67
    • CH-4102  Binningen
    • Switzerland
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    • Develco Pharma Schweiz AG
    • Ms.  Dr.  Martina  Maritz 
    • Hauptstrasse 67
    • CH-4102   Binningen
    • Switzerland
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Sources of Monetary or Material Support

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    • Develco Pharma Schweiz AG
    • CH-4102  Binningen
    • Switzerland
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Status

  •   Recruiting complete, follow-up complete
  •   2012/02/09
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Trial Publications, Results and other Documents

  •   Lux et al., CMRO 30(11) 2014, 2365-2375 "Clinical evaluation of the first oxycodone once daily prolonged release tablet in moderate to severe chronic pain: a randomized, double-blind, multicenter, cross-over, non-inferiority study to investigate efficacy and safety in comparison with an established oxycodone twice daily prolonged release tablet"
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* This entry means the parameter is not applicable or has not been set.