Efficacy and Safety Study of Gabapentin as add-on to Morphine in Paediatric Patients Affected by Chronic Pain

NCT03275012 | Withdrawn Phase 2 DMC

• 1 other identifier: 2014-004897-40
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of the study is to evaluate the efficacy of gabapentin as adjunctive therapy to morphine in the treatment of severe chronic neuropathic or mixed pain in children from 3 months to less than 18 years of age assessed by the difference in average pain scores between treatment arms at the end of the treatment period.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Pain scores

  Pain scores in the two treatment groups assessed at baseline and at the end of the treatment by age-appropriate pain scales. FLACC (the Faces, Legs, Arms, Cry and Consolability - pts aged 3-24 months) scale composed by 5 categories. Each category is scored on the 0-2 scale, which results in a total score of 0-10, where 0=Relaxed and comfortable, 4-6=Moderate pain, 1-3=Mild discomfort, 7-10=Severe discomfort or pain or both. FPS-R scale (Faces Pain Scale - Revised - pts aged 3-7 years): score is associated with face 0, 2, 4, 6, 8, or 10, where 0 = no pain and 10=very much pain. NRS-11(Numerical Rating Scale - pts aged 8-17 years): numerical rating scale where 0=no pain and 10=worst possible pain

  on average of 16 weeks

Secondary Outcomes (32)

• Percentage of responders to treatments

  on average of 16 weeks

• Daily pain intensity

  an average of 3 weeks

• Observational assessment of pain

  on average of 16 weeks

• Self-assessment of pain for children ≥8 years of age

  on average of 16 weeks

• Extent of pain

  on average of 16 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

Gabapentin + Morphine

Drug: Gabapentin + Morphine

Group 2

PLACEBO COMPARATOR

Placebo + Morphine

Drug: Placebo + Morphine

Interventions

Gabapentin + Morphine DRUG

Gabapentin: liquid oral formulation (syrup) - 75 mg/ml-three times daily. The starting dose during the optimization period will be defined according to 2 weight groups (5-15kg and \>15kg). Dose will be scaled at Day 1,3,5,14,and 21 according to a specific schedule. Maintenance dosing will be scheduled in accordance to the body weight. Morphine: background therapy as oral, liquid and solid formulations. Patients with BW≤30kg :liquid oral formulation four times daily throughout the whole treatment period. Patients with BM\>30kg : immediate release solid and/or liquid oral formulation four times daily during titration phase and an extended release solid oral formulation twice daily during the maintenance period.

Group 1

Placebo + Morphine DRUG

Placebo liquid oral formulation. Morphine: background therapy as oral, liquid and solid formulations. Patients with BW≤30kg :liquid oral formulation four times daily throughout the whole treatment period. Patients with BM\>30kg : immediate release solid and/or liquid oral formulation four times daily during titration phase and an extended release solid oral formulation twice daily during the maintenance period.

Group 2

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female, aged 3 months to less than 18 years at screening (V1)
• Informed consent by parent(s) and/or legal guardian according to each country legal requirement.
• Assent, where applicable, according to each country legal requirement.Informed (co-) consent of child, where applicable, according to each country legal requirement.
• Subjects that meet the diagnostic criteria for neuropathic or mixed pain.
• Subjects that present with chronic pain defined as the recurrent or continuous pain persisting more than 3 months.
• Subject that present with severe pain as defined by average pain intensity of ≥7 /10 as assessed during a 3-day screening period
• Stable underlying disease condition and treatment.
• Patients with Chemotherapy Induced Peripheral Neuropathy, when in clinical remission or maintenance phase of their therapeutic protocol.

You may not qualify if:

• Pain duration of more than 5 years.
• Current use of gabapentin.
• Current use of strong opioids (morphine, methadone, fentanyl, ketamine, oxycodone).
• History of failure to respond to adequate treatment by gabapentin or opioids for neuropathic pain.
• History of epileptic condition (except febrile seizure disorder).
• Subjects with diagnosis of sickle cell disease.
• Subjects that present significant cognitive impairment.
• Subjects that present current, controlled or uncontrolled, co-morbid psychiatric diagnosis that can impair pain diagnosis and assessment such as severe depressive conditions or psychosis.
• Subjects with history of or current suicidal ideation or behaviour.
• Subjects with history of substance abuse in particular opioids.
• Subjects under prohibited concomitant medication .
• Subjects with a body mass index (BMI) for age and gender of \< 5th percentile or \> 95th percentile (charts provided as Appendix 3).
• Subjects with significant renal impairment, i.e., glomerular filtration rate \< 90 mL/min/1.73 m2 (Revised Schwarz equation).
• Subjects with significant hepatic impairment or with Aspartate Transaminase (AST) or Alanine Transaminase (ALT) enzymes 3 times the upper limit of the age-specific reference range.
• Subjects in need for corticosteroid oral treatment or corticosteroid infiltrations to treat pain caused by infiltration or compression of neural structures, e.g. peripheral nerves or spinal cord.

Sponsors & Collaborators

• Pharmaceutical Research Management srl: lead
• European Commission: collaborator

Related Publications (3)

• Finnerup NB, Sindrup SH, Jensen TS. Recent advances in pharmacological treatment of neuropathic pain. F1000 Med Rep. 2010 Jul 14;2:52. doi: 10.3410/M2-52.

  PMID: 21170362 BACKGROUND

• Mellegers MA, Furlan AD, Mailis A. Gabapentin for neuropathic pain: systematic review of controlled and uncontrolled literature. Clin J Pain. 2001 Dec;17(4):284-95. doi: 10.1097/00002508-200112000-00002.

  PMID: 11783808 BACKGROUND

• de Leeuw TG, Mangiarini L, Lundin R, Kaguelidou F, van der Zanden T, Pasqua OD, Tibboel D, Ceci A, de Wildt SN; GAPP consortium. Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial. Trials. 2019 Jan 15;20(1):49. doi: 10.1186/s13063-018-3169-3.

  PMID: 30646965 DERIVED

Related Links

• The Task force in Europe for Drug Development for the Young (TEDDY) is a network of excellence funded in 2005 as a consortium responding to a call published by the European Commission.

MeSH Terms

Conditions

Chronic Pain

Interventions

Gabapentin; Morphine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Saskia De Wildt, MD-PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2017
• First Posted: September 7, 2017
• Study Start: April 4, 2017
• Primary Completion: October 21, 2019
• Study Completion: October 21, 2019
• Last Updated: December 2, 2019

Record last verified: 2019-11