Painful Diabetic Neuropathy
Conditions
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Male or female outpatients at least 18 years of age. 2. Clinical diagnosis of type 1 or type 2 diabetes mellitus. 3. Distal symmetric sensorimotor polyneuropathy defined by any of the following abnormalities: • Bilateral impaired or absent reflexes at the ankles • Bilateral impaired vibration, pinprick, fine touch or temperature perception in the distal lower extremities Note: Specific nerve conduction velocity findings are not required for inclusion. 4. A hemoglobin A1c concentration 5 years can be included if a documented diagnosis of diabetic neuropathy by a neurologist exists. 7. Baseline pain intensity scores averaging = 5.0 during the Baseline Phase and at least four days of pain (PI-NRS >0) recorded during the last seven days of that phase. 8. If female, the subject is eligible to enter and participate in this study if she is not lactating and is of: a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal [defined as one year without menses]); or, b. child-bearing potential, has a negative urine pregnancy test at screen (prior to investigational product administration), and agrees to one of the acceptable methods of contraception as noted in Section 14.3., “Appendix 3: Acceptable Methods of Contraception”. 9. Is able to understand the study procedures, schedule and able to comply with study requirements including use of acetaminophen/paracetamol only as rescue analgesia, completion of electronic-diary, and questionnaires without assistance as well as walking 50 feet (15 meters) during a visit without help. 10. A signed and dated written informed consent is obtained from the subject or the subject’s legally acceptable representative prior to study participation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Subject has other pain condition(s) not associated with painful diabetic neuropathy. However, the subject will not be excluded if the pain condition is: • at a different region of the body AND • the intensity of the pain is not greater than the intensity of the painful diabetic neuropathy. 2. Lower extremity pain of any severity due to mononeuropathy, osteoarthritis of the ankle or foot, gout, bursitis, or fasciitis. 3. Diffuse peripheral neuropathy attributable to other causes (e.g., alcoholism, malignancy, HIV, syphilis, drug abuse, peripheral ischemia, B-12 deficiency, hypothyroidism, liver disease, toxic exposure, significant focal neuropathy in the lower extremities, or acute or chronic poly-radiculopathy. 4. Pain attributed to focal or multifocal diabetic neuropathies including mononeuropathies of the cranial nerve, trunk and limb, entrapment or asymmetric lower limb motor neuropathy (amyotrophy) or symmetric proximal lower limb motor neuropathy (amyotrophy). However, the subject will not be excluded from study participation if amyotrophic pain has resolved after at least one year and the current pain is due to distal symmetric sensorimotor polyneuropathy. 5. Multiple sclerosis or other conditions commonly associated with central neuropathic pain. 6. Unable to discontinue prohibited medications 2 weeks prior to the time of investigational product administration and throughout the duration of the study. (Note: Adenosine, topical capsaicin applied for the relief of target pain or intrathecal peptides must be discontinued 4 weeks prior to the time of investigational product administration and throughout the duration of the study. 7. Initiation of a new analgesic for continuous use throughout the study is not allowed. However, short-term use of NSAID or COX-2 inhibitor analgesics for new, acute conditions can be added for pain not related to painful diabetic neuropathy for up to 7 days. 8. Nerve blocks or acupuncture for the relief of diabetic neuropathic pain performed four (4) weeks prior to the time of investigational product administration and throughout the duration of the study. 9. Non-drug therapies or any other special procedures (e.g. TENS) administered for the relief of diabetic neuropathic pain 2 weeks prior to the time of investigational product administration and throughout the duration of the study. (TENS administered for pain removed from the site of diabetic neuropathic pain is acceptable.) 10. Presence of any condition, physical examination finding or laboratory test result which, in the opinion of the investigator, could interfere with the evaluation of the subject, accurate completion of the symptom scale, interpretation of efficacy or safety data, or compliance with the protocol requirements. This includes, but is not limited to: • Skin conditions at site of neuropathy that could alter sensation • Lower extremity amputations other than toes • Active infection at site of neuropathy 11. Medical history or clinical evidence of major depression or a psychiatric condition that would interfere with safe participation in this study. A subject with major depression controlled by selective serotonin reuptake inhibitors will not be excluded from study participation. 12. Subject has a history of clinically significant drug or alcohol abuse, as defined by the Diagnostic and Statistical M
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of lamotrigine (LTG) extended release compared with placebo for the treatment of pain associated with diabetic neuropathy.;Secondary Objective: • To evaluate the safety of LTG extended release dosed at compared with placebo for the treatment of pain associated with diabetic neuropathy. • To evaluate the effect of LTG extended release versus placebo on quality of life, daily functioning, sleep, pain intensity with 50-foot (15-meter) walk and anxiety. • To characterize the population pharmacokinetics of LTG extended release in subjects with painful diabetic neuropathy and to assess the presence of a pharmacokinetic/pharmacodynamic relationship between systemic LTG exposure and clinical outcome.;Primary end point(s): Change in pain intensity score from baseline (average of the Baseline Phase pain intensity scores) to the last week of the Maintenance Phase treatment (average of the last week of the Maintenance Phase pain intensity scores), measured by the 11-point Pain Intensity Numerical Rating Scale. | — |
Countries
Denmark, Latvia
Outcome results
None listed