| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 effect of SB681323 on the clinical signs of neuropathic pain in patients with nerve trauma and/or compression |
|
| E.2.2 | Secondary objectives of the trial |
•To investigate the effect of SB681323 on experimental psychophysical measures of sensitisation in pain pathways in patients with nerve trauma and/or compression
•To investigate the effect of SB681323 on specific measures of the TRPV1 pathway in patients with nerve trauma and/or compression
•To investigate the value of these additional exploratory endpoints for future studies in neuropathic pain patients
•To assess the safety of SB681323 in patients with neuropathic pain
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female subjects 18-80 years of age
2. To be eligible, females patients must be of:
a. non-childbearing potential (i.e. physiologically incapable of becoming pregnant).
This includes any female who is post-menopausal. For the purposes of this study,
post menopausal is defined as being amenorrhoeic for greater than 2 years with an
appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms.
Postmenopausal status will be confirmed by serum FSH and oestradiol
concentrations at screening. Surgical sterility will be defined as females who have
had a hysterectomy and/or bilateral oophorectomy or tubal ligation.
OR
b. childbearing potential and have a negative pregnancy test and agree to commit to
one of the protocol-approved methods of contraception, when used consistently and
in accordance with both the product label and the instructions of a physician, as
indicated below:
i. oral contraceptive (combined or progestin only), and the same oral contraceptive
regimen has been used for at least two months prior to study drug administration, and the same method continues throughout the study and through the follow-up phase of the study.
ii. progesterone implanted rods (e.g. Norplant ) inserted for at least two months prior to the study drug administration (but not beyond the third successive year following insertion) , and is continued throughout the study and through the follow-up phase of the study.
iii. an IUD, inserted by a qualified clinician, with published data showing that the
highest expected failure rate is less than 1% per year (not all IUDs meet this
criterion) Acceptable IUDs: TCu-380A (Paragard), TCU-380 Slimline (Gyne T
Slimline), TCu-220C, MULTILOAD-250 (MLCu-250), 375 and 375 SL, Nova T
and Cunovat (Novagard), Levonorgesterol (LNG-20) Intra-uterine System
(Mirena/Levonova), and FlexiGard 330/CuFix PP330 (Gynefix). The device must
be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and through the follow-up phase of the study.
iv. injectable medroxyprogesterone acetate (e.g., Depo-Provera) and is on a stable dose for 2 months prior to Screen, throughout the study and through the follow-up phase of the study.
v. complete abstinence from intercourse from at least two weeks prior to Screen,
throughout the treatment phase, and the follow-up phase.
vi. double barrier method if comprised of a spermicide with either a condom or
diaphragm from at least two weeks prior to Screen, throughout the treatment phase,
and the follow-up phase.
3. A diagnosis of peripheral neuropathic pain:
• focal neuropathic pain related to nerve injury caused by trauma or surgery not
associated with ongoing infection (examples include post-thoracotomy
syndrome, post-mastectomy syndrome, post-inguinal herniorrhaphy syndrome,
post-radical neck dissection syndrome, traumatic mononeuropathies- bullet
wounds, lacerations, road traffic accidents)
• pain associated with lumbo-sacral radiculopathy; patients with radiculopathy
will only be included if they have pain radiating to or below the knee and have
loss of small fibre function as indicated by quantitative sensory testing (warm
sensation >9.6 0C or cool sensation >5.6 0C in L4, L5 or S1 dermatomes)
[Quraishi, 2004]. The figures refer to change from the thermode baseline (see
Section 6.8.4 for details).
• carpal tunnel syndrome (CTS); patients with CTS will only be included if there
is evidence of loss of large and/or small fibre function (confirmed by an
electrophysiological nerve conduction examination or by quantitative sensory
testing - warm sensation >5.2 0C or cool sensation >4.5 0C - in median nerve
territory) (Anand et al, unpublished data). The figures refer to change from the
thermode baseline (see Section 6.8.4 for details).
• location of pain consistent with the area innervated by the affected nerve(s),
with or without other sensory symptoms in the affected area
• at least 3 months duration
4. Baseline pain intensity score averaging 4 during the three days prior to
randomisation as reported on the 11 point pain intensity numerical rating scale. For
CTS patients, peak daily pain will be ≥4 for at least 3 days prior to randomisation.
5. Subjects who have received nerve blocks or steroid injections for neuropathic pain
may be included if their most recent nerve block was at least 4 weeks prior to
randomisation.
6. Body weight ≥50 kg (110 lbs) for men and ≥45 kg for women, Body Mass Index
18.5-35kg/m2.
7. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within
normal limits at screening.
8. Subjects must have a QTc(b) of less than 450msecs for males and females or less
than 480msecs for patients with bundle branch block at screening.
9. The subject is able to understand and comply with protocol requirements,
instructions & protocol-stated restrictions.
10. Signed and dated written informed consent prior to admission to the study. |
|
| E.4 | Principal exclusion criteria |
1. Any clinically significant medical history or abnormality found on physical
examination, laboratory assessment or ECG at screening which, in the opinion of the
investigator, could interfere with the interpretation of efficacy or safety data or which
otherwise would contraindicate participation in a clinical study, in particular:
• subjects with non-neuropathic pain component involvement, mononeuropathy
multiplex, or more than one cause or potential cause for pain symptoms (e.g.
trigeminal neuralgia, painful diabetic neuropathy, central post-stroke pain, phantom
limb pain, peripheral neuropathy due to alcoholism, malignancy, HIV, syphilis, drug
abuse, vitamin deficiency, hypothyroidism, liver disease, toxic exposure, or chronic
neck pain);
• subjects with intractable pain of unknown origin or active infection in the area of
nerve injury/compression;
• subjects who have had extensive soft tissue injury associated with extensive surgery
in the treatment of their nerve injury. Any question regarding the definition of
extensive surgery should be discussed with the GSK medical monitor;
• history of Gilbert's syndrome or elevated bilirubin levels (total, direct or indirect) in
a previous clinical study or at screening;
• history of increased liver function tests (ALT, AST) above upper limit of normal in
the past 6 months;
• positive Hepatitis B surface antigen, positive Hepatitis C antibody or Hepatitis C
nucleic acid result;
• GI disorders that may interfere with safety assessments, e.g. diarrhoea.
2. Recent start or change in dosing regimen (≤1 month prior to randomisation) of any medication which, in the opinion of the Investigator, may interfere with pain
assessments or introduce a risk of drug-drug interactions (see Section 9.2, Prohibited
Medications for details). Subjects may continue to take medications for the treatment
of their neuropathic pain as long as the regimen is stable and does not contain
prohibited medications.
3. Unable to refrain from excessive use medications (e.g. sedatives) that in the opinion of Investigator may interfere with efficacy or safety assessments (benzodiazepines prescribed as hypnotic sleep agents allowed). Subject is unable to discontinue topical analgesics prior to randomization and for the duration of the study (see Section 9.2, Prohibited Medications for details).
4. Subject is unable to refrain from nerve blocks during the study.
5. Positive alcohol test or urine drug screen at screening. 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.
6. History of regular alcohol consumption exceeding an average weekly intake of > 21 units (or an average daily intake of greater than 3 units) for males, or an average
weekly intake of > 14 units (or an average daily intake of greater than 2 units) for
females.
7. Donation of blood in excess of 500 mL within a 30-day period prior to dosing.
8. Participation in a trial with any drug within 3 months before the start of the study or
participation in a trial with a new chemical entity within 4 months before the start of
the study.
9. Pregnant or nursing female subjects.
10. Known history of hypersensitivity or intolerance to paracetamol products.
11. Inability or unwillingness to follow the instruction of the study protocol.
12. An unwillingness of male subjects to abstain from sexual intercourse with women; or unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception (as described in inclusion criterion for women) if the woman could become pregnant from the time of the first dose of investigational product until completion of the follow-up procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Average daily pain score based on the 11 point pain intensity numeric rating scale, NRS (0=no pain, 10 maximum pain imaginable) over Week 1 and Week 2 of the treatment |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
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