Chronic PainPhase 3GABA-1NCT02722603
Study to Compare Gabapentin to Tramadol in Children With Chronic Neuropathic or Mixed Pain
A Phase 3 study testing gabapentin and tramadol in people with Chronic Pain, run by Pharmaceutical Research Management srl at 2 sites in 2 countries.
Trial summary
This study evaluates the efficacy and safety of gabapentin relative to tramadol for the treatment of chronic, neuropathic or mixed pain in the paediatric population. Children from 3 months to less than 18 years of age experiencing moderate to severe chronic pain will receive either gabapentin or tramadol for 15 weeks. Read more about this study
- Who is it for?
- Ages 3 months to 17 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- gabapentin and tramadol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 12 Sep 2018to 18 Jun 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female, aged 3 months to less than 18 years at screening.
- Informed consent by parent(s) and/or legal guardian according to each country legal requirement.
- Assent by the patient, 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. Duration of pain will be determined from the date of the first pain experienced.
- Subjects that present with at least moderate pain as defined by average pain intensity of ≥4/10 as assessed during a 3-day screening period
- Stable underlying disease condition and treatment.
- In presence of malignant diseases, subjects in clinical remission and/or no expected changes in their therapeutic protocol during participation to the present study.
Who cannot join
- Pain duration of more than 5 years.
- Current use of gabapentin or tramadol.
- History of failure to respond to adequate treatment by gabapentin or tramadol/opioids for neuropathic pain.
- History of epileptic condition except febrile seizure disorder.
- Subjects with sleeping apnoea syndrome of any origin or subjects with history of severe respiratory impairment.
- Subjects with diagnosis of sickle cell disease.
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- 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 suicidal ideation or behaviour.
- History of substance abuse in particular opioids.
- Subjects under prohibited concomitant medication
- 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.
- Subjects born prematurely at ≤ 36 weeks gestational age, if recruited during the first year of age.
- Subjects with a body mass index (BMI) for age and gender of < 5th percentile or > 95th percentile.
- Subjects with glomerular filtration rate < 90 mL/min/1.73 m2 (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 with known allergy, hypersensitivity or clinically significant intolerance to gabapentin or tramadol or any component found in the study drugs.
- Subjects with fructose intolerance, diabetes, glucose-galactose malabsorption or lactase-isomaltase deficiency.
- Subjects with clinically relevant abnormal ECG at the screening visit in the discretion of the Investigator/cardiologist.
- Subjects participating in another clinical interventional trial.
- Subjects scheduled for surgery or in recovery from surgery occurring within 3 months of baseline assessment.
- Female subjects who are pregnant or currently lactating.
- Subjects that failed screening or were previously enrolled in this study.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Erasmus Universitair Medisch Centrum Rotterdam
Rotterdam
About this study
Official title: Randomized, Double-blind, Double-dummy, Active Controlled, Multicentre, Non-inferiority Phase-III Study to Compare Gabapentin Liquid Formulation to Tramadol in Children Experiencing Moderate to Severe Chronic Neuropathic or Mixed Pain
This study evaluates the efficacy and safety of gabapentin relative to tramadol for the treatment of chronic, neuropathic or mixed pain in the paediatric population. Children from 3 months to less than 18 years of age experiencing moderate to severe chronic pain will receive either gabapentin or tramadol for 15 weeks. The difference in average pain scores between treatment arms at the end of the treatment period will be assessed.
Read the detailed description
Gabapentin is indicated for the treatment of peripheral neuropathic pain in adults. In the absence of specific paediatric studies, it is not approved for the same condition in children.
The paediatric use of gabapentin is hampered by a) the lack of a suitable paediatric formulation, b) the significant variability of gabapentin pharmacokinetics profile and c) efficacy and safety data in this specific population.
The GABA-1 study is designed to demonstrate the efficacy of gabapentin oral solution relative to tramadol and to document the Pharmacokinetic and safety profile of gabapentin in this indication.
GABA-1 is a non-inferiority trial because gabapentin is expected to be equally effective but better tolerated than tramadol, thus providing a clinical benefit to affected children.
- Conditions
- Chronic Pain
- Being tested
- gabapentin, tramadol, placebo tramadol, placebo gabapentin
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gabapentinDrug
75 mg/ml gabapentin syrup
tramadolDrug
100 mg/ml tramadol oral drops
placebo tramadolOther
placebo tramadol oral drops
placebo gabapentinOther
placebo gabapentin syrup
| Study group | Role | What they receive |
|---|---|---|
| gabapentin / placebo tramadol | Experimental | gabapentin 75 mg/ml syrup / placebo tramadol, 3 times/day for 15 weeks. Receives: Drug: gabapentin; Other: placebo tramadol |
| tramadol / placebo gabapentin | Active comparator | tramadol oral drops 100 mg/ml / placebo gabapentin, 3 times/day for 15 weeks. Receives: Drug: tramadol; Other: placebo gabapentin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain score
Pain score (0-10) measured at baseline (before starting the therapy) and at the end of the treatment in: patients aged 3-24 months using FLACC pain scale, patients aged 3-7 years using FPS-R scale, patients aged 8-17 years using NRS-11.
The FLACC (the Faces, Legs, Arms, Cry and Consolability) scale is 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 (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.
Measured: an average of 16 weeks
Secondary outcomes (32)
Percentage of responders to treatment
Subjects with a pain intensity reduction of 30% from baseline or below or equal to 3/10, assessed by age-appropriate pain scale. FLACC (the Faces, Legs, Arms, Cry and Consolability) scale (pts aged 3-24-months) is 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 (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.
Measured: an average of 16 weeks
Daily pain intensity
Daily pain intensity, assessed by age-appropriate scale (FLACC, FPS-R or NRS-11) during dose optimization.
The FLACC (the Faces, Legs, Arms, Cry and Consolability) scale (pts aged 3-24-months) is 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 (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.
Measured: an average of 3 weeks
Observational assessment of pain
Observational assessment of pain using the NRS-11 completed by parents and Investigator (or caregiver) at each visit.
NRS-11: numerical rating scale where 0=no pain and 10=worst possible pain
Measured: an average of 16 weeks
Self-assessment of pain for children ≥8 years of age
Self-assessment of pain for children ≥8 years of age using the FPS-R pain scale at each visit.
FPS-R (Faces Pain Scale - Revised) Score is associated with face 0, 2, 4, 6, 8, or 10, where 0 = no pain and 10=very much pain.
Measured: an average of 16 weeks
Extent of pain
number of painful areas using the pain charts at screening visit (V1), randomisation (v2) and EOS visit (V10). The pain charts are body maps (front and back) in which each body section is identified with a number.
Measured: an average of 16 weeks
Number of episodes of breakthrough pain
Number of episodes of breakthrough pain (> 4/10 pain score and use of rescue medications) during treatment period.
Measured: an average of 16 weeks
Number of rescue interventions
Number of rescue interventions required during treatment period
Measured: an average of 15 weeks
Number of pain-free days
Number of pain-free (< 4/10 average pain score without the use of rescue medications) days during treatment period
Measured: an average of 15 weeks
Number of participant dropouts
Number of participant dropouts due to lack of efficacy
Measured: up to 21 weeks
The total cumulative weight normalized dose of each rescue drug
The total cumulative weight normalized dose of each rescue drug
Measured: up to 21 weeks
Total Summary Score from PedsQL™ scale
Total score obtained using the PedsQL 4.0 Generic Core Scales (by parent, patient aged 3-17years) and PedsQL Infants Scales (by parent of pts aged 3-24months) at randomisation (V2) and at EOS (V10). The total score is a measure of Health Related Quality of life (HRQoL). Higher scores indicate better HRQOL.
PedsQL 4.0 Generic Core Scales is composed by 4 multidimensional scales (Physical Funct, Emotional Funct, Social Funct, School Funct) and 3 summary scores (Total Scale Score, Physical Health Summary Score, Psychosocial Health Summary Score). Scoring is based on a 5-point Likert scale from 0 (Never) to 4 (Almost always).
PedsQL Infant Scales is composed by 5 multidim. scales (Physical Functioning, Physical Symptoms, Emotional Functioning, Social Functioning, Cognitive Functioning) and 3 summary scores (Total Scale Score, Physical Health Summary Score, Psychosocial Health Summary Score). The scoring is based on a 5-point Likert scale from 0 (Never) to 4 (Almost always)
Measured: an average of 15 weeks
Physical Health Summary Score from PedsQL™ scale
Physical Health Score obtained using the PedsQL™ 4.0 Generic Core Scales (by parent, patient aged 3-17 years) and PedsQL™ Infant Scales (by parent, aged 3-24 months) at randomisation (V2) and at EOS (V10).
PedsQL™ 4.0 Generic Core Scales is composed by 4 multidimensional scales (Physical Funct, Emotional Funct, Social Funct, School Funct) and 3 summary scores (Total Scale Score, Physical Health Summary Score, Psychosocial Health Summary Score). Scoring is based on a 5-point Likert scale from 0 (Never) to 4 (Almost always).
PedsQL™ Infant Scales is composed by 5 multidimensional scales (Physical Functioning, Physical Symptoms, Emotional Functioning, Social Functioning, Cognitive Functioning) and 3 summary scores (Total Scale Score, Physical Health Summary Score, Psychosocial Health Summary Score). The scoring is based on a 5-point Likert scale from 0 (Never) to 4 (Almost always).
Measured: an average of 15 weeks
Psychosocial Health Summary Score from PedsQL™ scale
Psychosocial Health Score obtained using the PedsQL™ 4.0 Generic Core Scales (by parent, patient aged 3-17 years) and PedsQL™ Infant Scales (by parent, aged 3-24 months) at randomisation (V2) and at EOS (V10).
PedsQL™ 4.0 Generic Core Scales is composed by 4 multidimensional scales (Physical Funct, Emotional Funct, Social Funct, School Funct) and 3 summary scores (Total Scale Score, Physical Health Summary Score, Psychosocial Health Summary Score). Scoring is based on a 5-point Likert scale from 0 (Never) to 4 (Almost always).
PedsQL™ Infant Scales is composed by 5 multidimensional scales (Physical Functioning, Physical Symptoms, Emotional Functioning, Social Functioning, Cognitive Functioning) and 3 summary scores (Total Scale Score, Physical Health Summary Score, Psychosocial Health Summary Score). The scoring is based on a 5-point Likert scale from 0 (Never) to 4 (Almost always).
Measured: an average of 15 weeks
Acceptability of treatment
Acceptability of treatment (Five-Point Facial Hedonic scale) at EOS visit (V10).
Each face in the scale is related to a score (1=unpleasant; 2=not sure; 3=pleasant).
Measured: at week 16
Global satisfaction with treatment
Global satisfaction with treatment (NRS-11, by parent, patient) at EOS visit (V10).
The satisfaction is measeured by the numerical rating scale NRS-11 where 0=not satisfied and 10=fully satisfied
Measured: at week 15
Clinical Global Impression of Severity of the subject's condition
Clinical Global Impression of Severity (CGI-S) for Neuropathic or Mixed Pain Overall Severity Prior to Study Treatment (at randomization - V2) assessed by Investigator.
Investigators will rate their impression of the severity of the subject's condition. Scoring: Normal: no signs of pain, Borderline painful, Mildly painful, Moderately painful, Markedly painful,Severely painful, Among the most extremely painful patients.
Measured: an average of 15 weeks
Clinical Global Impression of Improvement for pain
Clinical Global Impression of Improvement (CGI-I) for Neuropathic or Mixed Pain Overall at V6 and EOS visit (V10) assessed by Investigator.
Investigators will rate their impression of any change of the subject's overall condition of neuropathic or mixed pain since randomization in the study. Scoring are: Very much improved since the initiation of treatment; Much improved; Minimally improved; No change from baseline (the initiation of treatment); Minimally worse; Much worse; Very much worse since the initiation of treatment.
Measured: an average of 15 weeks
Patient/parent Global Impression of Change
Patient/parent Global Impression of Change (PGIC; by parent, patient) at V6 and at EOS visit (V10).
Patient/parent will rate their impression of any change of the subject's overall condition of neuropathic or mixed pain since randomization in the study. Scoring are: Very much improved since the initiation of treatment; Much improved; Minimally improved; No change from baseline (the initiation of treatment); Minimally worse; Much worse; Very much worse since the initiation of treatment.
Measured: an average of 12 weeks
CL/F
Primary pharmacokinetic parameters for gabapentin and tramadol: assessment of apparent clearance (CL/F) and of its variability and precision. In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
Vd/F
Primary pharmacokinetic parameter for gabapentin and tramadol: assessment of apparent volume of distribution (Vd/F) and of its variability and precision. In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
ka
Primary pharmacokinetic parameter for gabapentin and tramadol: assessment of absorption rate constant (Ka) and of its precision and variability. In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
AUC
Secondary pharmacokinetic parameter for gabapentin and tramadol: assessment of Area under the Concentration curve (AUC). In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
Cmax
Secondary pharmacokinetic parameter for gabapentin and tramadol: assessment of peak plasma concentration (Cmax). In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
Tmax
Secondary pharmacokinetic parameter for gabapentin and tramadol: assessment of time at which the Cmax is observed (Tmax). In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
Css
Secondary pharmacokinetic parameter for gabapentin and tramadol: assessment of steady state Concentrations (Css). In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
Cmin
Secondary pharmacokinetic parameter for gabapentin and tramadol: assessment of minimum concentration (Cmin). In total, 4 samples will be collected, 1 before dosing and again at 3 different time windows post-dosing (0 - 2 h; 2 - 4 h and 4 - 6 h)
Measured: at week 3 or at week 4 or at week 16
Systemic exposure to investigational products during maintenance period
Systemic exposure to investigational products during maintenance period, as assessed by predicted steady-state concentrations.
Measured: an average of 12 weeks
Incidence of Adverse Events at all visits
Incidence of Adverse Events at all visits
Measured: up to 21 weeks
Percentage of subjects discontinuing the trial due to treatment-emergent adverse events.
Percentage of subjects discontinuing the trial due to treatment-emergent adverse events.
Measured: up to 21 weeks
Aggressive behaviour in children aged >6 years
Aggressive behaviour in children aged >6 years using the Retrospective-Modified Overt Aggression Scale (R-MOAS) at V2, V6 and EOS visit (V10).
The scale includes 4 domains (Verbal Incidents, Incidents Toward Other People, Incidents Involving Property, Incidents Directed Toward Self) each one describing different behaviours.
Parents rate the frequency of 16 aggressive behaviors (referred to the past week) in the 4 areas. Numeric weighting amplifies the seriousness of more harmful behaviors in the total score. Higher score indicating more aggressive behavior.
Measured: an average of 15 weeks
Suicidal ideation/behaviour in subjects aged 6 years and older
Suicidal ideation/behaviour in subjects aged ≥ 6 years using the Columbia - Suicide Severity Rating Scale (C-SSRS) before IMP (screening V1), V6, EOS visit (V10) and end of taper visit (V11). The C-SSRS is divided into 2 sections: Suicidal Ideation and Suicidal Behaviour containing each one 5 "yes" or "no" questions.
Suicidal Ideation Score: The maximum suicidal ideation category (1-5 on the CSSRS) present at the assessment. A score of 0 is assigned if no ideation is present.
Composite endpoints are defined below:
Suicidal ideation: A "yes" answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5).
Suicidal behavior: A "yes" answer at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10).
Suicidal ideation or behavior: A "yes" answer at any time during treatment to any one of the ten suicidal ideation and behavior questions (Categories 1-10)
Measured: an average of 16 weeks
Assessment of blinding
Assessment of blinding: guess of the subject's treatment group (by Investigator, parents and subject if at adequate maturity level) at V10.
Measured: at week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2016 (estimated)
- Study start12 Sep 2018
- Primary completion31 May 2019
- Study completion18 Jun 2019
Why it stopped: The study was early terminated due to insufficient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmaceutical Research Management srl
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Florentia Kaguelidou, Principal investigator, Center Clin Investig INSERM CIC 1426 H. R Debré APH de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02722603
- Sponsor's protocol ID
- 2014-004851-30
- Other IDs
- 2014
- Acronym
- GABA-1
- Status last verified
- Sep 2019
- First submitted
- 18 Mar 2016
- Last updated
- 3 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 21170362Mellegers 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.
PubMed 11783808Kaguelidou F, Le Roux E, Mangiarini L, Lundin R, de Leeuw TG, Della Pasqua O, Felisi M, Bonifazi D, Tibboel D, Ceci A, de Wildt SN, Alberti C; GAPP consortium. Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol. BMJ Open. 2019 Feb 20;9(2):e023296. doi: 10.1136/bmjopen-2018-023296.
PubMed 30787078
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Double-dummy, Active Controlled, Multicentre, Non-inferiority Phase-III Study to Compare Gabapentin Liquid Formulation to Tramadol in Children Experiencing Moderate to Severe Chronic Neuropathic or Mixed Pain
- ClinicalTrials.gov ID
- NCT02722603
- Acronym / sponsor ID
- GABA-1 / 2014-004851-30
- Conditions
- Chronic Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was early terminated due to insufficient recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Pharmaceutical Research Management srlIndustry (pharma, biotech, devices)
- Collaborators
- European Commission
- Study start
- 12 Sep 2018 (actual)
- Primary completion
- 31 May 2019 (actual)
- Study completion
- 18 Jun 2019 (actual)
- First posted
- 30 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the efficacy and safety of gabapentin relative to tramadol for the treatment of chronic, neuropathic or mixed pain in the paediatric population. Children from 3 months to less than 18 years of age experiencing moderate to severe chronic pain will receive either gabapentin or tramadol for 15 weeks. The difference in average pain scores between treatment arms at the end of the treatment period will be assessed.
Detailed description
Gabapentin is indicated for the treatment of peripheral neuropathic pain in adults. In the absence of specific paediatric studies, it is not approved for the same condition in children.
The paediatric use of gabapentin is hampered by a) the lack of a suitable paediatric formulation, b) the significant variability of gabapentin pharmacokinetics profile and c) efficacy and safety data in this specific population.
The GABA-1 study is designed to demonstrate the efficacy of gabapentin oral solution relative to tramadol and to document the Pharmacokinetic and safety profile of gabapentin in this indication.
GABA-1 is a non-inferiority trial because gabapentin is expected to be equally effective but better tolerated than tramadol, thus providing a clinical benefit to affected children.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| gabapentin / placebo tramadol | Experimental | Drug: gabapentin, Other: placebo tramadolgabapentin 75 mg/ml syrup / placebo tramadol, 3 times/day for 15 weeks. |
| tramadol / placebo gabapentin | Active comparator | Drug: tramadol, Other: placebo gabapentintramadol oral drops 100 mg/ml / placebo gabapentin, 3 times/day for 15 weeks. |
Who may qualify
- Ages
- 3 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Male or female, aged 3 months to less than 18 years at screening.
- Informed consent by parent(s) and/or legal guardian according to each country legal requirement.
- Assent by the patient, 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. Duration of pain will be determined from the date of the first pain experienced.
Key exclusion criteria (23 listed)
- Pain duration of more than 5 years.
- Current use of gabapentin or tramadol.
- History of failure to respond to adequate treatment by gabapentin or tramadol/opioids for neuropathic pain.
- History of epileptic condition except febrile seizure disorder.
- Subjects with sleeping apnoea syndrome of any origin or subjects with history of severe respiratory impairment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gabapentin75 mg/ml gabapentin syrup | Drug | gabapentin / placebo tramadol |
| tramadol100 mg/ml tramadol oral drops | Drug | tramadol / placebo gabapentin |
| placebo tramadolplacebo tramadol oral drops | Other | gabapentin / placebo tramadol |
| placebo gabapentinplacebo gabapentin syrup | Other | tramadol / placebo gabapentin |
Primary outcome
Pain score
Time frame: an average of 16 weeks
Pain score (0-10) measured at baseline (before starting the therapy) and at the end of the treatment in: patients aged 3-24 months using FLACC pain scale, patients aged 3-7 years using FPS-R scale, patients aged 8-17 years using NRS-11. The FLACC (the Faces, Legs, Arms, Cry and Consolability) scale is 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 (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.
32 secondary outcomes
Percentage of responders to treatment
Time frame: an average of 16 weeks
Daily pain intensity
Time frame: an average of 3 weeks
Observational assessment of pain
Time frame: an average of 16 weeks
Self-assessment of pain for children ≥8 years of age
Time frame: an average of 16 weeks
Extent of pain
Time frame: an average of 16 weeks
Number of episodes of breakthrough pain
Time frame: an average of 16 weeks
Number of rescue interventions
Time frame: an average of 15 weeks
Number of pain-free days
Time frame: an average of 15 weeks
Number of participant dropouts
Time frame: up to 21 weeks
The total cumulative weight normalized dose of each rescue drug
Time frame: up to 21 weeks
Total Summary Score from PedsQL™ scale
Time frame: an average of 15 weeks
Physical Health Summary Score from PedsQL™ scale
Time frame: an average of 15 weeks
Psychosocial Health Summary Score from PedsQL™ scale
Time frame: an average of 15 weeks
Acceptability of treatment
Time frame: at week 16
Global satisfaction with treatment
Time frame: at week 15
Clinical Global Impression of Severity of the subject's condition
Time frame: an average of 15 weeks
Clinical Global Impression of Improvement for pain
Time frame: an average of 15 weeks
Patient/parent Global Impression of Change
Time frame: an average of 12 weeks
CL/F
Time frame: at week 3 or at week 4 or at week 16
Vd/F
Time frame: at week 3 or at week 4 or at week 16
ka
Time frame: at week 3 or at week 4 or at week 16
AUC
Time frame: at week 3 or at week 4 or at week 16
Cmax
Time frame: at week 3 or at week 4 or at week 16
Tmax
Time frame: at week 3 or at week 4 or at week 16
Css
Time frame: at week 3 or at week 4 or at week 16
Cmin
Time frame: at week 3 or at week 4 or at week 16
Systemic exposure to investigational products during maintenance period
Time frame: an average of 12 weeks
Incidence of Adverse Events at all visits
Time frame: up to 21 weeks
Percentage of subjects discontinuing the trial due to treatment-emergent adverse events.
Time frame: up to 21 weeks
Aggressive behaviour in children aged >6 years
Time frame: an average of 15 weeks
Suicidal ideation/behaviour in subjects aged 6 years and older
Time frame: an average of 16 weeks
Assessment of blinding
Time frame: at week 16
Results and safety
The study was stopped early (reason given: The study was early terminated due to insufficient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2019.
- Background: PubMed 21170362Finnerup 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.
- Background: PubMed 11783808Mellegers 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.
- Derived from this study: PubMed 30787078Kaguelidou F, Le Roux E, Mangiarini L, Lundin R, de Leeuw TG, Della Pasqua O, Felisi M, Bonifazi D, Tibboel D, Ceci A, de Wildt SN, Alberti C; GAPP consortium. Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol. BMJ Open. 2019 Feb 20;9(2):e023296. doi: 10.1136/bmjopen-2018-023296.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florentia Kaguelidou principal investigator
Center Clin Investig INSERM CIC 1426 H. R Debré APH de Paris
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing gabapentin and tramadol in people with Chronic Pain, run by Pharmaceutical Research Management srl at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was early terminated due to insufficient recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain score (time frame: an average of 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02722603, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2019.