Trial document

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Trial Description

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An Open-label Trial, Enrolling Subjects Aged 6 Years to Less Than 18 Years Suffering From Pain Requiring Prolonged Release Opioid Treatment, to Evaluate the Safety and Efficacy of Tapentadol PR Versus Morphine PR, Followed by an Open-label Extension.

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Trial Acronym


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URL of the Trial


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Brief Summary in Lay Language

Tapentadol has already been studied in adults. This study is needed to find out if
tapentadol works and is safe to use in children and adolescents with long-term pain.

During the first 2 weeks of the study (Part 1), participants will be given either tapentadol
or morphine prolonged-release tablets. Assignment will be done randomly (like tossing a
coin). The participant and the caregiver will know which medication they are taking. The
primary endpoint is based on data collected in Part 1 of this trial.

If eligible and willing, participants from Part 1 can enter a 12 month follow-up period
(Part 2). In Part 2 of this trial participants will be treated with tapentadol prolonged
release tablets or with the standard of care (observation arm).

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Brief Summary in Scientific Language


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Organizational Data

  •   DRKS00008574
  •   2015/05/21
  •   2014/05/28
  •   no
  •   [---]*
  •   [---]*
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Secondary IDs

  •   U1111-1154-4572 
  •   2012-004360-22 
  •   NCT02151682  (
  •   KF5503-66  (Grünenthal GmbH)
  •   2012-004360-22 
  •   U1111-1154-4572 
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Health Condition or Problem studied

  •   Pain
  •   R52 -  Pain, not elsewhere classified
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Interventions/Observational Groups

  •   Drug: Tapentadol prolonged release
  •   Drug: Morphine prolonged release
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  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group), Control group receives no treatment, Other
  •   Treatment
  •   Factorial
  •   II-III
  •   [---]*
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Primary Outcome

- Proportion of participants classified as responders; time frame: up to Day 14 (End of Part 1); Responders are participants who meet both of the following criteria:
Completion of the 14-day Treatment Period (Part 1).
One of the following calculated from the scheduled pain assessments ("pain right now") documented during the last 3 days of the Treatment Period:
Average pain less than 50 on a visual analog scale (VAS) for subjects aged 12 years to less than 18 years; or less than 5 on the Faces Pain Scale-revised (FPS-R) for subjects aged 6 years to less than 12 years.
Average reduction from baseline of pain greater than and equal to 20 on a VAS for subjects aged 12 years to less than 18 years; or greater and equal to 2 on the FPS-R for subjects aged 6 years to less than 12 years.

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Secondary Outcome

- Constipation; time frame: Day 1; Day 14 (End of Part 1); Constipation will be assessed using the modified constipation assessment scale (CAS). This is an 8-item questionnaire where the observer will score constipation on a nominal scale (no problem, some problem or severe problem). The response to an item could also be scored as "unable to assess".
- Tolerability; time frame: Day 1 (Start of Part 1); Day 379 (End of Part 2); Tolerability will be assessed by the number and type of adverse events and adverse drug reactions by treatment group during the different trial periods, on a participant and event level.

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Countries of Recruitment

  •   Belgium
  •   France
  •   Germany
  •   Slovakia
  •   Spain
  •   United Kingdom
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Locations of Recruitment

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  •   [---]*
  •   2014/12/31
  •   200
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   6   Years
  •   17   Years
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Additional Inclusion Criteria

Part 1 - Randomized to open-label, active comparator controlled treatment

Participants are eligible for the trial at if all the following apply:

- Informed consent (if applicable assent) obtained.

- Male or female participant at least 6 years of age at the Enrollment Visit and less
than 18 years of age on Day 14.

- Participant has an underlying long-term pain condition that is, according to the
judgment of the investigator, expected to require a twice-daily prolonged release
opioid treatment until at least the end of the 14-day Treatment Period.

- Participant can swallow tablets of appropriate size.

- Participant is able to participate in the trial as planned and willing to comply with
the requirements of the protocol including refraining from drinking beverages
containing alcohol and recreational intake of drugs while on study medication.

Participants must satisfy the following criteria before allocation to treatment:

- Less than 18 years of age.

- No opioid intake or last calculated morphine equivalent dose of less than 3.5 mg/kg
per day.

- Participant has a body weight of at least 17.5 kg.

- If a female of childbearing potential (post menarchal and not surgically incapable of
childbearing) and sexually active, must practice an effective method of birth control
(e.g., prescription oral contraceptives, contraceptive injections, intrauterine
device, double barrier method, contraceptive patch) before allocation to study
medication until the end of intake of study medication.

- If a female and post menarchal or older than 12 years, has a negative urine pregnancy
test on the day before or on the day of allocation to study medication.

Part 2

Inclusion criteria for the Tapentadol Open-label extension period:

- Participant has completed the 14-day Treatment Period.

- Participant is still in need of prolonged release opioid treatment.

- Participant does not meet any of the compulsory discontinuation criteria.

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Exclusion Criteria

Participants are not eligible for the trial if any of the following apply.

The following will be checked at enrollment:

- Has been previously enrolled in this trial or a previous trial with tapentadol.

- Has a clinically relevant history of hypersensitivity, allergy, or contraindication
to morphine or tapentadol or any ingredient, including galactose intolerance (see
investigator's brochure for tapentadol PR and summary of product characteristics for
morphine PR), or naloxone.

- History or current condition of any one of the following:

- Seizure disorder or epilepsy.

- Serotonin syndrome.

- Traumatic or hypoxic brain injury, brain contusion, stroke, transient ischemic
attack, intracranial hematoma, posttraumatic amnesia, brain neoplasm, or
episode(s) of more than 24 hours duration of unconsciousness.

- History or current condition of any one of the following:

- Moderate to severe renal or hepatic impairment.

- Abnormal pulmonary function or clinically relevant respiratory disease (e.g.,
acute or severe bronchial asthma, hypercapnia)

- History of alcohol or drug abuse in the investigator's judgment, based on history and
physical examination. Drugs of abuse detected in urine screen unless explained by
allowed concomitant medication

- Participant has:

- A clinically relevant abnormal electrocardiogram.

- Signs of pre-excitation syndrome.

- Brugada's syndrome.

- QT or QTcF (Fridericia) interval greater than 470 ms.

- Any surgery scheduled during the first 14 days of the trial that is expected to
require post-surgical intensive care unit (ICU) treatment, or that requires
post-surgical parenteral pain-treatment, or may, affect the safety of the

- Participant is not able to understand and comply with the protocol as appropriate for
the age of the subject or subject is cognitively impaired in the investigator's
judgment such that they cannot comply with the protocol.

- Participant, parent or the legal representative is an employee of the investigator or
trial site, with direct involvement in the proposed trial or other studies under the
direction of that investigator or trial site, or family member of the employees or
the investigator.

The following will be checked at the enrollment and the allocation visits:

- Has a concomitant disease or disorder (e.g., endocrine, metabolic, neurological,
psychiatric, infection) that in the opinion of the investigator may affect or
compromise subject safety during the trial participation.

- Pancreatic/biliary tract disease (e.g., pancreatitis) or paralytic ileus.

- Intake of forbidden concomitant medication/use of forbidden therapies (see synopsis
section Concomitant medications/therapies).

The following will be checked at the allocation to treatment visit:

- Has received a drug or used a medical device not approved for human use within 30
days prior to visit.

- Based on data from the local laboratory, one or more of:

- Total serum bilirubin greater than 2.0 mg/dL.

- Serum albumin less than 2.8 g/dL.

- Aspartate transaminase or alanine transaminase greater than 5 times upper limit
of normal.

- Based on data from the local laboratory, creatinine clearance less than 30 mL/min per
1.73 m2 (calculated according to a formula that is appropriate for the respective age

- If the participant suffers from non-cancer related pain: participation in any
interventional clinical trial within 30 days prior to visit.

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  • start of 1:1-Block address primary-sponsor
    • Grünenthal GmbH
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    •   [---]*
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    • Grünenthal GmbH
    • Director Clinical Trials 
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    •   [---]*
    •   [---]*
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    • Grünenthal Trial Information Desk 
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Sources of Monetary or Material Support

  • [---]*
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  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in and DRKS are not identical. Therefore the data import from required adjustments. For full details please see the DRKS FAQs .
  •   4
  •   2015/05/19
* This entry means the parameter is not applicable or has not been set.