Neuropathic pain associated with diabetic peripheral neuropathy MedDRA version: 17.0 Level: LLT Classification code 10067547 Term: Diabetic peripheral neuropathic pain System Organ Class: 100000004852
Conditions
Interventions
Product Code: CNV2197944
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not assigned
Other descriptive name: CNV2197944C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
Convergence Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent. 2. A female patient 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 amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. Patients having other severe pain, which may impair the self-assessment of the pain due to DPN. 2. Diabetic related medical conditions that might impair the assessment of pain due to DPN. This would include amputations, major skin ulcers, physical injury to the affected limb, or any planned surgeries during the course of the study. 3. Patients who have received nerve blocks for neuropathic pain within 4 weeks prior to the start of the single-blind placebo run-in (Day 1). 4. Certain medications used to relieve the pain of DPN such as gabapentanoids, tricyclic antidepressants, SNRIs, anticonvulsants/antiepileptics, opioids, topical analgesics, capsaicin products, mexiletine, dextromethorphan, tramadol, cannabinoids, ketamine and oral/injectable corticosteroids are prohibited during the study and must be washed out prior to the start of the run-in period (Day 1). 5. Patients with a documented failure to respond to a maximum tolerated dose regimen of gabapentin or pregabalin. The dose should fall within the approved regulatory labelling for DPN for this exclusion to apply. In case of uncertainty the case should be discussed with the medical monitor. 6. Use of other prohibited medications. 7. History or presence of significant cardiovascular or gastro-intestinal 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 patient safety. In case of uncertainty the case should be discussed with the medical monitor. 8. A positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result. 9. History of regular alcohol consumption during the 6 months prior to screening, defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units for male patients and of greater than 14 units weekly or an average daily intake of greater than 2 units for female patients. One unit is equivalent to a half-pint (280 mL) of beer or 1 (25 mL) measure of spirits or 1 glass (125 mL) of wine. 10. A significant medical history of recurrent syncope or symptomatic orthostatic hypotension, blackouts, fainting or vaso-vagal attacks during the twelve months prior to screening, or evidence of low blood pressure at screening or baseline (systolic BP 2x upper limit of normal. Alkaline phosphatase or bilirubin >1.5x upper limit of normal. 16. Creatinine cleara
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of repeat oral dosing of CNV2197944 on neuropathic pain in patients with diabetic peripheral neuropathy (DPN).;Secondary Objective: Secondary Objectives: To investigate the effects of repeat oral dosing of CNV2197944 75 mg tid on overall global function in patients with pain from DPN. To investigate the safety and tolerability of CNV2197944 in patients with DPN. To assess the blood concentrations and exposures of CNV2197944. Exploratory Objectives: To explore the frequency of genetic mutation in sodium and calcium channels in DPN and the relationship to response to CNV2197944.;Primary end point(s): Change in average daily neuropathic pain score between the third week of treatment and baseline based on the 11 point PI-NRS (0=no pain, 10=maximum pain imaginable.) Subjects should specifically rate the pain intensity for the neuropathic pain associated with DPN and not pain from other causes. ;Timepoint(s) of evaluation of this end point: Change from baseline following 3 weeks of active treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: The following endpoints specifically refer to the neuropathic pain from DPN. • Change in average daily pain score from baseline over time (weeks 1, 2 and 3 of treatment). • Change in Neuropathic Pain Symptom Inventory total score and sub-scales from baseline to week 3 of treatment. • = 30% reduction in PI-NRS score after 3 weeks of treatment. • = 50% reduction in PI-NRS score after 3 weeks of treatment. • Improved Patient Global Impression of Change (PGIC) after 3 weeks of treatment. • Improved Clinician Global Impression of Change (CGIC) after 3 weeks of treatment. Safety: • Incidence, severity, seriousness and relatedness of adverse events. • Changes in laboratory safety test results (clinical chemistry, haematology, urinalysis) and the incidence of abnormal laboratory test results. • Changes in blood pressure and heart rate. • Changes in ECG parameters. Pharmacokinetics: • Pre-dose and post-dose blood CNV2197944 concentrations – AUC(0-24)-ss, Cmin-ss and Cmax-ss. Exploratory Endpoints: • Total dose of paracetamol taken during treatment periods as a rescue medication for DPN pain only. • Presence of genetic mutations in sodium channel (Nav1.1, Nav1.2, Nav1.3, Nav1.6 and Nav1.7) or calcium channel (Cav2.2 and Cav2.1) genes (optional). ;Timepoint(s) of evaluation of this end point: 3 weeks of active treatment. | — |
Countries
Bulgaria, Czech Republic, Hungary, Poland
Contacts
Public ContactClinical Trials Information
Convergence Pharmaceuticals Ltd
Outcome results
None listed