A Study to Look at Tapentadol Tablets in Children and Adolescents in Pain

NCT02151682 | Completed Phase 2 Results DMC

• 3 other identifiers: KF5503-662012-004360-22U1111-1154-4572
• Study Type: interventional
• Target: 73
• Locations: 10 countries
• Sites: 23

Brief Summary

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.

Conditions

Pain

Keywords

chronic pain; opioid

Outcome Measures

Primary Outcomes (1)

• Number of Participants Classified as Responder (Part 1)

  The proportion of participants classified as responders was assessed and compared between the treatment groups. A participant was defined as responder if both of the following criteria were met: * 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, range 0 \[no pain\] to 100 \[pain as bad as it could be\]) for participants aged 12 years to less than 18 years; or less than 5 on the Faces Pain Scale-revised (FPS-R, range 0 \[no pain\] and 10 \[very much pain\]) for participants aged 6 years to less than 12 years. * Average reduction from baseline of pain greater than or equal to 20 on a VAS for participants aged 12 years to less than 18 years; or greater than or equal to 2 on the FPS-R for participants aged 6 years to less than 12 years.

  From Day 1 up to Day 14 (End of Part 1)

Secondary Outcomes (2)

• Extent of Constipation (Part 1)

  From Day 1 to Day 14 (End of Part 1)

• Tolerability Over the Complete Trial Period

  Part 1: Day 1 (Start of Part 1) to Day 14; Part 2: Day 15 to Day 379 (End of Part 2)

Other Outcomes (16)

• Change in Pain Intensity in the Open-label, Active-controlled Treatment Period (Part 1)

  From Baseline up to Day 14 (End of Part 1) or early discontinuation

• Change in Pain Intensity in the Tapentadol Open-label Extension Period (Part 2)

  From Day 15 to Day 379 (End of Part 2)

• Use of Rescue Medication in the Open-Label, Active-controlled Treatment Period (Part 1)

  From Day 1 up to Day 14 (End of Part 1)

Study Arms (6)

Morphine prolonged-release (Part 1)

ACTIVE COMPARATOR

10 milligram (mg) or 30 mg tablets were taken orally twice daily. Starting doses varied from 10 to 40 mg morphine PR twice daily depending on participant's weight; if necessary, doses were gradually increased up to a maximum dose defined per weight group. The highest dose defined for participants weighing 55 kg and more was 200 mg per day.

Drug: Morphine prolonged release

Tapentadol prolonged-release (Part 1)

EXPERIMENTAL

25 mg or 100 mg tablets were taken orally twice daily. Starting doses varied from 25 to 100 mg tapentadol PR twice daily depending on participant's weight. If necessary, doses were gradually increased up to a maximum dose defined per weight group. The highest dose defined for participants weighing 55 kg and more was 500 mg per day.

Drug: Tapentadol prolonged release

Tapentadol in Part 2 after Tapentadol or Morphine in Part 1

EXPERIMENTAL

Participants on tapentadol PR in Part 1 of the study continued on the current dose of tapentadol PR in Part 2 and if necessary could modify their tapentadol PR dosage. Participants who were randomized to morphine PR in Part 1 of the study were rotated to tapentadol PR in Part 2 with 70 percent of their current morphine equivalent dose or lower. The dosage could be increased gradually up to approximately 4.5 mg/kg body weight tapentadol PR twice daily.

Drug: Tapentadol prolonged release

Observation Period after Tapentadol in Part 1

NO INTERVENTION

Participants who completed tapentadol PR in Part 1 of the study or discontinued tapentadol treatment early in Part 1 could continue directly in the observation period in Part 2 for up to 12 months (with standard-of-care treatment if needed).

Observation Period after Morphine in Part 1

NO INTERVENTION

Participants who completed morphine PR treatment in Part 1 of the study or discontinued early from morphine treatment in Part 1 could continue directly in the observation period in Part 2 (with standard-of-care treatment if needed).

Observation Period after Tapentadol in Part 2

NO INTERVENTION

Participants who completed tapentadol PR or morphine PR treatment in Part 1 of the study could enter the Observation Period for up to 12 months (with standard-of-care treatment if needed) after they had discontinued from tapentadol PR treatment in Part 2.

Interventions

Tapentadol prolonged release DRUG

Also known as: Palexia®, Nucynta®, Yantil®

Tapentadol in Part 2 after Tapentadol or Morphine in Part 1; Tapentadol prolonged-release (Part 1)

Morphine prolonged release DRUG

Morphine prolonged-release (Part 1)

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Part 1 - Randomized to open-label, active comparator controlled treatment
• Participants were eligible for the study at enrollment if all the following applied:
• 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 (e.g., cancer, chronic disease, planned or performed surgery) 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 study 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 had to 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
• Participant has completed the 14-day Treatment Period.

You may not qualify if:

• Participants were not eligible for the study if any of the following applied.
• The following was checked at enrollment:
• Has been previously enrolled in this study or a previous study 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 prolonged-release \[PR\] 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)
• Complex regional pain syndrome.
• A pain indication with a strong psycho-somatic component that, in the judgment of the investigator, is unlikely to respond to opioids.
• 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:

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (23)

BE001

Leuven, 3000, Belgium

Location

BG005

Pleven, 5800, Bulgaria

Location

BG004

Plovdiv, 4001, Bulgaria

Location

BG001

Sofia, 1606, Bulgaria

Location

BG006

Sofia, 1606, Bulgaria

Location

CL004

Santiago, 7500996, Chile

Location

CL001

Valparaíso, 2341131, Chile

Location

FR008

Amiens, 80054, France

Location

FR004

Brest, 29609, France

Location

FR002

Lille, 59020, France

Location

FR006

Lyon, 69008, France

Location

FR005

Nice, 06200, France

Location

FR001

Vandœuvre-lès-Nancy, 54500, France

Location

FR003

Villejuif, 94805, France

Location

DE001

Homburg, 66421, Germany

Location

HU001

Budapest, 1094, Hungary

Location

IT003

Turin, 10126, Italy

Location

PT001

Braga, 4710-243, Portugal

Location

PT002

Porto, 4200-319, Portugal

Location

ES003

Valladolid, 47005, Spain

Location

GB005

Leeds, LS1 3EX, United Kingdom

Location

GB003

Manchester, M13 9WL, United Kingdom

Location

GB006

Sheffield, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Pain; Chronic Pain

Interventions

Tapentadol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Clinical Trial Helpdesk
• Organization: Grünenthal GmbH

clinical-trials@grunenthal.com

+49-(0)241-569

Study Officials

• Director Clinical Trials

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There were 2 arms in Part 1: Randomization was carried out in blocks and in a 2:1 ratio (tapentadol PR to morphine PR). Participants were stratified using interactive response technology: by age group (6 years to less than 12 years and 12 years to less than 18 years, at the second visit \[Allocation Visit\]) so that at least 25% of participants were in the younger age group, and by underlying pain condition (cancer/non-cancer-related pain). There were 4 arms in Part 2: The investigators/participants decided if participants from Part 1 switched to or continued on tapentadol PR (tapentadol arm) or if they received no treatment/standard of care treatment if needed (2 direct observation arms following treatment in Part 1 and 1 observation arm after initial treatment with tapentadol in Part 2).

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Study Start: April 29, 2015
• Primary Completion: October 18, 2017
• Study Completion: October 15, 2018
• Last Updated: September 12, 2019
• Results First Posted: September 12, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

HU (1); IT (1); DE (1); CL (2); FR (7); BU (4); PT (2); BE (1); GB (3); ES (1)