Primary objectiveThe primary objective of this study is to assess the efficacy of gabapentin relative to tramadol for the treatment of moderate to severe chronic neuropathic or mixed pain in children from 3 months to less than 18 years of age.…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Average pain score at the end of the treatment period (average of 2 measures
each day for 3 days before end of study visit, V10) as assessed by
age-appropriate pain scales (FLACC, FPS-R, NRS-11).
Secondary outcome
Secondary endpoints
a) Percentage of responders to treatments, defined as subjects with a 30%
reduction from baseline in assessment scale (FLACC, FPS-R, NRS-11).
b) Average daily pain intensity assessed by age appropriate scale during dose
optimisation (FLACC, FPS-R or NRS-11).
c) Observational assessment of pain using the NRS-11 completed by parents and
Investigator (or caregiver) at each visit.
d) Self-assessment of pain for children >8 years of age using the FPS-R pain
scale at each visit.
e) Number of episodes of breakthrough pain (> 4/10 pain score and use of rescue
medications) during treatment period.
f) Number of rescue interventions required during treatment period.
g) Number of pain-free (< 4/10 average pain score without the use of rescue
medications) days during treatment period.
h) Number of participant dropouts due to lack of efficacy.
i) The total cumulative weight normalized dose of each rescue drug.
j) Quality of life, physical, emotional, social and school functioning and
quality of sleep on the PedsQL Generic Core Scales (by parent, patient)
assessed at randomisation (V2) and at EOS (V10).
k) Acceptability of treatment (Five-Point Facial Hedonic scale) at EOS visit
(V10).
l) Global satisfaction with treatment (NRS-11, by parent, patient) at EOS visit
(V10).
m) Clinical Global Impression of Change (CGI-S, CGI-I; by Investigator) at
randomisation (V2) for CGI-S and V6 and EOS visit (V10) for CGI-I.
n) Patient/parent Global Impression of Change (PGIC; by parent, patient) at V6
and at EOS visit (V10).
o) Primary (CL/F, Vd/F, Ka) and secondary (AUC, Cmax, Tmax, Css and Cmin)
pharmacokinetic parameters for gabapentin and tramadol.
p) Systemic exposure to investigational products during maintenance period, as
assessed by predicted steady-state concentrations.
q) Incidence of Adverse Events at all visits.
r) Percentage of subjects discontinuing the trial due to treatment-emergent
adverse events.
s) Aggressive behaviour in children aged >6 years using the
Retrospective-Modified Overt Aggression Scale (R-MOAS) at V2, V6 and EOS visit
(V10).
t) Suicidal ideation/behaviour in subjects aged 6 years and older using the
Columbia - Suicide Severity Rating Scale (C-SSRS) scores before IMP (screening
V1), V6 and at the EOS visit (V10).
u) Assessment of blinding: guess of the subject*s treatment group (by
Investigator, parents and subject if at adequate maturity level) at V10.
Exploratory endpoints
v) Metabolomic profile at screening (V1) and at EOS visit (V10), and in
responders and non-responders.
w) PK or PD outcomes based on genetic variation.
Background summary
Gabapentin has been successfully used to treat neuropathic pain in adults and
has been used offlabel
to treat children with the same condition.
However, the paediatric use of gabapentin in children is hampered by two main
factors:
1. The lack of a suitable oral formulation
2. The significant variability of gabapentin PK profile demonstrated in
children less than 4
years of age leading to a variable drug plasma concentration. These differences
should be taken
into account to define a safe/efficacious dosing regimen in younger children.
Study objective
Primary objective
The primary objective of this study is to assess the efficacy of gabapentin
relative to tramadol for the treatment of moderate to severe chronic
neuropathic or mixed pain in children from 3 months to less than 18 years of
age.
Secondary objectives
1. To assess effect of gabapentin relative to tramadol on quality of life
(physical, emotional,
social and school functioning) and global satisfaction with treatment.
2. To assess safety of gabapentin relative to tramadol for treatment of chronic
neuropathic or
mixed pain in children 3 months to less than 18 years of age.
3. To characterise the population pharmacokinetic-pharmacodynamic (PKPD)
relationship of
gabapentin liquid formulation and provide confirmation of the recommended
paediatric dose.
Additional exploratory objectives of the study are:
4. To describe the metabolomic profile following drug treatments.
5. To explore genetic polymorphisms and their impact on pharmacokinetics (PK)
and
pharmacodynamics (PD).
6. To assess the population pharmacokinetics of tramadol and, if feasible, its
PKPD relationship
in the paediatric population.
Study design
Randomized, double-blind, double-dummy active controlled, multicentre
non-inferiority phase-III study to compare efficacy and safety of gabapentin
liquid formulation to tramadol in children from 3 months to less than 18 years
of age experiencing moderate to severe chronic neuropathic or mixed pain.
Intervention
IMP test: Gabapentin oral solution (syrup) at 75 mg/ml
IMP comparator: Tramadol oral drops at 100 mg/ml
Study burden and risks
Uncontrolled pain may have a substantial impact on a child*s daily life and
lead to absence at
school, decreased quality of life decreased physical exercise, depression and
anxiety and social
isolation. Lack of timely treatment may lead to a lifetime of chronic pain.
There is a well-recognised need to improve management of chronic pain in
children.
All patients in this trial will receive pharmacological analgesic treatment and
therefore may
experience better pain relief with less adverse events, due to pre-defined and
controlled titration
of the study drugs as well as close monitoring of pain and adverse events. To
limit the occurrence
and severity of the side effects, the dose will be up-titrated slowly and
down-titration is allowed
when side effects are unacceptable.
The level of pain may increase during the wash-out period. We believe this is
acceptable, because current treatment has proved to be ineffectieve in
adequately decreasing pain levels after all. Thus increase in painscore due to
the interruption of paintreatment is expected to be limited. Children that
experience sufficient comfort under current pain treatment do not qualify for
participating in this study.
The risks of venipuncture are minimal.
Via Einstein Loc Cascina Codazza
Lodi 26900
IT
Via Einstein Loc Cascina Codazza
Lodi 26900
IT
Listed location countries
Age
Inclusion criteria
1. informed consent
2. 3 months - 18 years of age
3. meet the diagnostic criteria for neuropathic or mixed pain
4. chronic pain defined as the recurrent or continuous pain persisting more than 3 months
5. at least moderate pain as defined by average pain intensity of *4 /10
6. Stable underlying disease condition and treatment
7. For oncology patients: clinical remission or no expected changes in therapeutic protocol
Exclusion criteria
1. Pain duration of more than 5 years
2. Current use of gabapentin or tramadol for treatment of neuropathic pain or exposure in the year before screening for the GABA-1 study.
3. History of failure to respond to adequate treatment by gabapentin or tramadol/opioids for neuropathic pain.
4. History of epileptic condition except febrile seizure disorder.
5. Subjects with diagnosis of sickle cell disease.
6. Subjects that present significant cognitive impairment.
7. 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.
8. Subjects with history of suicidal ideation or behaviour.
9. Subjects under prohibited concomitant medication (refer to specific protocol section 6.6.2 *Prohibited medications*).
10. 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.
11. Subjects aged 3 months to less than 18 years old with a body mass index (BMI) for age and gender of < 5th percentile or > 95th percentile (charts provided as Appendix 5).
12. Subjects with glomerular filtration rate < 90 mL/min/1.73 m2 (Schwarz equation).
13. Subjects with significant hepatic impairment with Aspartate Transaminase (AST) and Alanine Transaminase (ALT) enzymes 3 times the upper limit of the age-specific reference range.
14. Subjects with known allergy, hypersensitivity or clinically significant intolerance to gabapentin or tramadol or any component found in the study drugs.
15. Subjects with clinically relevant abnormal ECG at the screening visit in the discretion of the investigator/cardiologist.
16. Subjects participating in another clinical interventional trial.
17. Subjects scheduled for surgery or in recovery from surgery occurring within 3 months of baseline assessment.
18. Female subjects who are pregnant or currently lactating.
19. Subjects that failed screening or was previously enrolled in this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-004851-30-NL |
| CCMO | NL55805.078.16 |