| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Neuropathic pain from lumbosacral radiculopathy |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037779 |
| E.1.2 | Term | Radiculopathy |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To investigate the effects of repeat oral dosing of GW856553 on neuropathic pain in
subjects with lumbosacral radiculopathy. |
|
| E.2.2 | Secondary objectives of the trial |
1. To investigate the effects of repeat oral dosing of GW856553 on low back pain in
subjects with lumbosacral radiculopathy.
2. To investigate the effects of repeat oral dosing of GW856553 on sleep, daily
function and mood in subjects with pain from lumbosacral radiculopathy.
3. To investigate the safety and tolerability of GW856553 in subjects with lumbosacral
radiculopathy.
4. To assess the pharmacokinetics of GW856553 (for patient compliance purposes
only). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female subjects aged 18 – 80 years inclusive, at the time of signing the
informed consent.
2. A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented
tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrheaview protocol for further information.
• Child-bearing potential and agrees to use one of the contraception methods listed
in Section 8.1 view protocol for further information.
3. A diagnosis of neuropathic pain due to lumbosacral radiculopathy with the following
characteristics1:
• Pain perceived in one or both lower limbs at sites consistent with the area innervated by the L4, L5 or S1 nerve
roots, with or without other sensory symptoms in the affected areas; (typically, the pain may be perceived in the
buttock, thigh, calf, leg, foot or toes).
• History of the pain suggestive that the cause of lumbosacral radiculopathy is due
to injury of the lumbosacral nerve root(s) , view protocol for further information.
• Duration of pain should be at least 12 weeks since onset.
• Intensity of pain should be stable for the 2 weeks prior to Screening, based on
clinical history.
• As part of the neurological examination, the investigator must also conduct the
procedures specified in the Standardised Evaluation of Pain and to calculate the total score. View protocol for
further information.
- Pain/sensory disturbance in dermatomal/myotomal distribution precipitated or
exacerbated by straight leg raising (the straight leg raising test should be
performed as specified in StEP;
- Neurological examination of lower limbs shows impaired muscle power,
sensory function or deep tendon reflexes in the territory of the affected nerve
roots;
- The total StEP score is ≥4 (indicative of lumbosacral radiculopathy as the
cause of the pain);
- Electromyographic (EMG) evidence of denervation in muscles innervated by
the affected nerve roots;
- Quantitative sensory tests (QST) showing evidence of altered sensory
thresholds in dermatomes innerved by the affected nerve roots;
At Screening, if the investigator is satisfied with the diagnosis based on clinical
review, or if results from such investigations related to the current symptoms are
already documented in the medical notes, then it is not essential for the
investigator to conduct computerised tomography (CT)/magnetic resonance imaging (MRI), EMG or QST. View protocol for further information.
However, all subjects who are considered eligible by the Investigator on clinical
grounds but have not had an CT/MRI undertaken to support the diagnosis of LSR
prior to Screening or where a previous CT/MRI scan is not available to the
Investigator, are required to have an CT/MRI undertaken during the
screening/baseline period (Day -28 to Day -1) view protocol for further information.
4. Subjects on medications for neuropathic pain (view protocol) may only be included in the study if they have
been on stable doses of such medications for at least 4 weeks prior to baseline period (Day -7).
5. Subjects who have not received NSAIDs, COX-2 inhibitors and/or topical lidocaine
for at least 5 half-lives or 2 weeks, whichever is longer prior to the baseline period
(Day -7), and for subjects who have not received topical capsaicin for at least 8
weeks prior to the baseline period.
6. Subjects who have not received nerve blocks and/or steroid injections for neuropathic pain for at least 4 weeks
prior to the baseline period (Day -7).
7. Subjects’ baseline average daily pain score for neuropathic pain due to LSR on the
PI-NRS, calculated as the average of their daily PI-NRS scores over the baseline
period (Day -7 to Day -1), is greater than or equal to 4 on the PI-NRS, after wash-out
of prohibited medications view protocol.
8. Male subjects must agree to use the contraception methods listed in Section 8.1.
This criterion must be followed from the time of the first dose of study medication
until 14 days after the last dose of study medication.
9. Body weight ≥ 50 kg for men and ≥ 45 kg for women.
10. Subject has provided full written informed consent prior to the performance of any protocol-specified
procedure, which includes compliance with the requirements and restrictions listed in the consent form.
11. Single QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle
Branch Block. If the first QTc exceeds the above limits, repeat the ECG twice at
least 5 min apart and take the mean of the three QTc values to determine that the
mean QTc satisfies the above limits.
12. A subject with a clinical abnormality or other laboratory parameters outside the
reference range for the population being studied may be included view protocol for further information. |
|
| E.4 | Principal exclusion criteria |
1. Subjects who, in the opinion of the Investigator, are unable to reliably delineate or
assess their own pain by anatomical location/distribution (e.g. can the subject
reliably tell the difference between their back pain and their lower limb pain and rate
their intensity separately ?).
2. Subjects with lumbar canal stenosis in which the pain in the lower limbs occur solely on walking and not at
rest.
3. Subjects with causes for their neuropathic pain other than that specified in Inclusion Criterion 3 view protocol,
pain associated with a substantial somatic pain component [e.g.non-neuropathic /musculoskeletal pain in
lower limbs or other parts of the body apart from the back] or more than one cause or potential cause for pain symptoms or any concurrent rheumatic disease such as but not limited to fibromyalgia, rheumatoid arthritis or
significant osteoarthritis. Any question regarding the acceptability of aetiology of the neuropathic pain should be
discussed with the GSK medical monitor.
4. A positive pre-study drug/alcohol screen. However, a positive drug screen will not
automatically exclude a subject if there is a medical explanation for the positive
result other than drug abuse e.g. a subject who is taking opioids for their neuropathic pain.
5. A positive test for HIV antibody or positive history of HIV.
6. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening
7. History of any liver disease within the last 6 months [with the exception of known
Gilbert’s disease].
8. History of excessive regular alcohol consumption within 6 months of the study
defined as outlined in protocol.
9. History or presence of significant cardiovascular, gastro-intestinal, or renal disease
or other condition known to interfere with the absorption, distribution, metabolism,
or excretion of drugs which, in the opinion of the Investigator may interfere with the
study procedures or compromise subject safety.
10. History or presence of any clinically significant abnormality in vital signs / ECG /
laboratory tests, or have any medical or psychiatric condition, which, in the opinion
of the Investigator, may interfere with the study procedures or compromise subject
safety.
11. Subject has clinical evidence of recent major depression (by medical history) except those subjects already
controlled by anti-depressants at screening.
12. Subjects who, in the clinical judgement of the investigator, may be malingering or be motivated by secondary
gain from participation in the study will be excluded. View protocol for further information.
13. Changes to medications permitted for the treatment of neuropathic pain (Section 9.1) within 4 weeks of the
baseline period (Day -7), including dose adjustment,
withdrawal of medications or initiation of new medications.
14. Subjects who are unable to maintain the same medications for the treatment of
neuropathic pain at the same stable dose as at baseline during the study.
15. Unable to refrain from excessive use of sedative medications (e.g. benzodiazepines
prescribed as hypnotics) that in the opinion of the Investigator may interfere with
efficacy or safety assessments.
16. Use of other prescription or non-prescription drugs, within 7 days (or 14 days if the drug is a potential enzyme
inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication (Day 1) or during the
study, view protocol for further information.
17. Unable to stop and remain abstained from non-pharmacological treatments for their neuropathic pain during
the study as specified in Section 9.3.
18. The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the baseline period (Day -7) in the
current study: 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).
19. Exposure to more than four new chemical entities within 12 months prior to the first dosing day (Day 1).
20. History of hypersensitivity to GW856553 or its components thereof or a history of
drug or other allergy that, in the opinion of the investigator or GSK Medical
Monitor, contraindicates their participation.
21. Where participation in the study would result in donation of blood or blood products in excess of 500 mL
within a 56 day period.
22. Pregnant females as determined by positive urine or serum hCG test at screening or prior to dosing.
23. Lactating females.
24. Unwillingness or inability to follow the procedures outlined in the protocol.
25. Subject is mentally or legally incapacitated.
26. Subjects with conditions requiring immunosuppressive therapy, or otherwise
considered immunosuppressed. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Change in average daily neuropathic pain score from baseline to Week 5 of treatment based on the 11 point Pain
Intensity Numerical Rating Scale (PI-NRS) (0=no pain, 10=maximum pain imaginable). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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