Chronic non-malignant neuropathic pain MedDRA version: 17.1 Level: PT Classification code 10029223 Term: Neuralgia System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Ketamine hydrochloride (HCl) prolonged-release (PR) tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ketamine
Other descriptive name: KETAMINE HYDROCHLORIDE
Concentr
Sponsors
Develco Pharma Schweiz AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients =18 years of age at Visit 1 (Screening) 2. Patients with a documented history of chronic non-malignant neuropathic pain at Visit 1 3. Patients with a DN4 Neuropathic Pain Diagnostic Questionnaire score of =4 at Visit 1 4. Stable individual regular standard treatment regimen for chronic neuropathic pain, i.e. no change in drug and non-drug treatments for at least two weeks prior to Visit 1 and anticipated to remain stable until the end of the single-blind treatment phase. Use of rescue medication for neuropathic pain (including topical treatments, physical measures etc.) or any other co-medication used on an “as-needed” basis that might affect pain perception or pain intensity as well as opioids as part of the regular standard treatment are not allowed in this trial. 5. Patients with inadequate pain control (mean “current” PI on VAS >50 mm) by their current individual standard treatment regimen on at least three days of the seven-day screening phase (to be checked at Visit 2) 6. Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the trial, including use of medication, completion of subjective evaluations, attending scheduled visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing signed written informed consent at Visit 1 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity or intolerance to ketamine or any of the excipients 2. Patients treated with any other ketamine preparation within the last month prior to Visit 1 3. Patients receiving opioids , regardless if as part of their individual standard treatment regimen for chronic neuropathic pain or in context with any other indication, within the last two weeks prior to Visit 1 4. Patients with untreated or uncontrolled arterial hypertension (sitting systolic blood pressure at rest =160 mmHg and/or sitting diastolic blood pressure at rest =90 mmHg) 5. History of cerebrovascular event (stroke, PRIND, TIA) within the previous six months prior to Visit 1 6. Known or suspected cardiac disease, especially coronary artery disease (e.g. unstable angina, congestive heart failure), tachyarrhythmia and history of myocardial infarction 7. Known or suspected hypovolemia or dehydration 8. Known or suspected hyperthyroidism or patients receiving thyroid replacement therapy within the last two weeks prior to Visit 1 9. Concomitant treatment with theophylline or aminophylline within the last two weeks prior to Visit 1 10. Long-term therapy for any chronic disease, if suspected to be unstable during the course of the trial 11. Regular or intermittent intake of St. John’s wort (hypericum perforatum), if not stopped at Visit 1 12. Other non-drug treatments such as physical measures, acupuncture, etc., if not stable since at least two weeks prior to Visit 1 or suspected to be unstable during the course of the trial 13. Known or suspected globe injury or increased intraocular pressure (e.g. glaucoma) 14. Known or suspected cranio-cerebral trauma, intracranial mass lesions, hydrocephalus or elevation of intracranial pressure within the last three months prior to Visit 1 or sequelae of previous events 15. Known or suspected convulsive disorder 16. Known or suspected acute intermittent porphyria 17. History or presence of moderate or severe psychiatric disorder (e.g. moderate or severe depression, schizophrenia or acute psychosis) 18. Known or suspected current pulmonary or upper respiratory infection 19. Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis 20. History of any malignancy in the last five years; except history of in-situ cancer or basal or squamous cell skin cancer. Patients with other malignancies are eligible if they have been continuously disease free for at least five years 21. Known or suspected CNS depression (signs/symptoms: decreased vital signs, impaired thinking and perception, slurred speech, slowed reflexes, fatigue, decreased consciousness) 22. History of drug addiction or drug seeking behaviour, positive test of illicit drugs (other than medication used for individual standard treatment of pain) at Visit 1 23. Surgery within one month, denervation procedures within six months or neural blockade (e.g. injection of a local anaesthetic into or near to a nerve), neuromodulatory measures (e.g. TENS) or radiotherapy two weeks prior to trial Visit 1 and/or anticipated and/or scheduled during the course of the trial 24. Evidence of impaired hepatic function (total bilirubin, AST, ALT, GGT, or AP >3 times the upper limit of normal) 25. Evidence of moderate or severe renal impairment (CRCL <60 ml/min) or patients with renal failure who are on any form of dialysis 26. Any gastro-intestinal pathology or surgery or intractable vomiting likely to significantly influence drug absorption 27. Inability to swallow
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to investigate the effect of Ketamine HCl PR tablets administered twice daily as add-on therapy to the individual standard treatment regimen of each patient in comparison to placebo in the relief of chronic non-malignant neuropathic pain as determined by absolute changes in the “current” pain intensity (PI) score on the visual analogue scale (VAS).;Secondary Objective: Secondary objectives are to investigate the effect of Ketamine HCl PR tablets administered twice daily as add-on therapy to the individual standard treatment regimen of each patient in comparison to placebo in improvement of symptoms of chronic non-malignant neuropathic pain as determined by relative changes in the “current” PI score on the VAS, as well as by absolute and relative changes in the Neuropathic Pain Symptom Inventory (NPSI), “recalled” average PI during the day and “recalled” average PI during the night. Moreover, a secondary objective is to assess the safety and tolerability of Ketamine HCl PR tablets administered twice daily as add-on therapy to the individual standard treatment regimen in patients with chronic non-malignant neuropathic pain. ;Primary end point(s): Primary end point is defined as the absolute change from baseline in “current” PI on 0 - 100 mm VAS (mean of all “current” PIs of the last four days of each treatment period) after Ketamine HCl PR Placebo tablets versus Ketamine HCl PR tablets.;Timepoint(s) of evaluation of this end point: Primary end point is evaluated at the end of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • relative change from baseline in “current” PI on 0 – 100 mm VAS (mean of all “current” PIs of the last four days of each treatment period) after Ketamine HCl PR Placebo tablets versus Ketamine HCl PR tablets • absolute and relative change from baseline in NPSI total intensity score and NPSI sub-scores after Ketamine HCl PR Placebo tablets versus Ketamine HCl PR tablets • absolute and relative change from baseline in “recalled average PI during the day on 0 – 100 mm VAS (mean of all “recalled” PIs during day-time of the last four days of each treatment period) after Ketamine HCl PR Placebo tablets versus Ketamine HCl PR tablets • absolute and relative change from baseline in “recalled average PI during night on 0 – 100 mm VAS (mean of all “recalled” PIs during night-time of the last four days of each treatment period) after Ketamine HCl PR Placebo tablets versus Ketamine HCl PR tablets • adverse events (AEs) • vital signs, standard laboratory evaluations, electrocardiogram (ECG) and physical examinations • the rate of discontinuations due to AEs during the active treatment phase (defined as the time from the first ketamine intake in Period 2 until the last ketamine intake in Period 3). ;Timepoint(s) of evaluation of this end point: Secondary end points are evaluated at the end of the trial. In addition, an interim review based on safety and tolerability outcomes (mainly occurrence of AEs) will occur after stage 1, in order to determine dosing levels for stage 2 as outlined in the protocol. | — |
Countries
Germany, Hungary
Contacts
Public ContactClinical Trial Manager
Develco Pharma Schweiz AG
Outcome results
None listed