Efficacy Study With 500 mg QD of TRO19622 vs Placebo in Patients With Painful Peripheral Diabetic Neuropathy

• 24h Pain time course [ Time Frame: Duration of study (within 11weeks after screening) ] [ Designated as safety issue: Yes ]
• Analysis for treatment effects: SF-MPQ, SF-BPI, SF36, POMS, Global Impression of Change (Patient / Investigator) [ Time Frame: Within 6 weeks of treatment ] [ Designated as safety issue: Yes ]
• Adverse events [ Time Frame: During the course of the study. ] [ Designated as safety issue: Yes ]

• 24h Pain time course [ Time Frame: Duration of study (within 11weeks after screening) ]
• Analysis for treatment effects: SF-MPQ, SF-BPI, SF36, POMS, Global Impression of Change (Patient / Investigator) [ Time Frame: Within 6 weeks of treatment ]
• Adverse events [ Time Frame: During the course of the study. ]

The purpose of this study is to assess the efficacy and safety of TRO19622 administered PO daily for 6 weeks compared to placebo administered PO daily in patients with painful peripheral diabetic neuropathy.

Diabetic peripheral neuropathic pain (DPNP) affects approximately 11% of patients with diabetic peripheral neuropathy (DPN). Diabetic neuropathy as the underlying disease is the most common long-term complication of diabetes mellitus estimated to be experienced by a majority of patients at least in a mild manner.

Many patients with (DPNP) do not respond adequately to any individual treatment option. None of the various treatments used can be considered a cure. As a result, although a variety of drugs are available for the treatment of diabetic neuropathic pain, there is a strong need to develop new drugs with greater efficacy and/or fewer adverse effects.

The primary objective of the study is to compare the effect of TRO19622 versus placebo on the 24h neuropathic pain scores during the last 7 days of the 6-week treatment period.

Secondary objectives are to compare the efficacy on neuropathic pain, impact on emotional functioning, safety profile, pain time course, and response rate of TRO19622 versus placebo. Additionally, the pharmacokinetics of TRO19622 will be assessed.

• Drug: Experimental
  Capsules of TRO19622 (125 mg)- Once a day before noon meal during 6 weeks
• Drug: Placebo comparator
  4 Capsules of PBO per day before noon meal

• Experimental: 1
  TRO19622
  Intervention: Drug: Experimental
• Placebo Comparator: 2
  Intervention: Drug: Placebo comparator

Inclusion Criteria:

• Be a male >18 years or a post-menopausal female (>60 years of age and at least 1 year of amenorrhea).
• Have painful diabetic neuropathy of >6 months duration and are either pain treatment naive or have important side effects or inadequate relief from their current pain medication.
• Be on current pain medication (prescribed analgesics), stable for at least 3 months before study entry (± 25% dosage of basic pain medication, top-up rescue medication allowed), or pain treatment naive.
• Have stable diabetes, defined as HbA1c <10%, no changes in medication in the previous 3 months, and no new symptoms associated with diabetes in the previous 3 months.
• Have scored >2 points on the Michigan Neuropathy Screening Instrument (MNSI), part B-physical assessment by health professional.
• Have an ECG without any clinically significant abnormality.

The following inclusion criteria should be ascertained at the baseline visit:

• Have measurable pain perception (previous 24h) on the Likert numerical rating scale with a mean≥4.0 points calculated from at least 4 daily measurements over the 7 days immediately prior to the Baseline Visit.
• Have stopped current pain medication at least 14 days prior to the Baseline Visit (except rescue medication).

Exclusion Criteria:

• Be pregnant female, lactating female, or female of child bearing potential (≤60 years of age).
• Have a documented neuropathy of any cause other than those mentioned in the inclusion criteria which might interfere with the assessment of the severity of pain (eg, including, but not limited to, alcoholic, uremic, B12, TSH, chemotherapy, HIV, post surgical, or post-traumatic neuropathy).
• Have other neurological diseases that may produce weakness, sensory loss, or autonomic symptoms, or laboratory test abnormality.
• Have been on pain treatment with strong opioids, more than 4 different drug regimens in the previous year, or a current combination of more than 2 drugs.
• Have a current medication of lipid lowering agents other than statins.
• Have a body mass index (BMI) >40 kg/m2 (obesity grade III).
• Had any surgery within the previous 2 months.
• Have concurrent serious neurological disease (eg, dementia, multiple sclerosis, or any other disease that would impact the ability of the patient to provide consent for study participation).
• Have a recent history (within the previous 6 months) or current evidence of alcohol or drug abuse.
• Have concurrent unstable disease involving any system (eg, advanced carcinoma, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency i.e.≥ NYHA functional classification class 2, anginal symptoms, current symptoms of CAD, renal impairment, or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation).
• Participated in any other investigational drug or therapy study within the previous 3 months.
• Changed or interrupted current well-tolerated medication during the previous 3 months.
• Lack of ability or willingness to give informed consent.
• Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).
• Have hemostasis disorders or a current treatment of anticoagulants.

• Have non-adequate renal and/or hepatic function as follows:

  • Renal - Blood creatinine >1.5X upper limit of normal (ULN)
  • Hepatic - Liver enzymes (ALT and AST) >2 X ULN
• Have a known history of or current cardiac dysrhythmias and / or a known history of or current cardiovascular disease including myocardial infarction except patients with well controlled hypertension only.
• Are not able to comply with regard to the known contraindications, warnings and precautions, drug-interactions and dosing recommendations of paracetamol.