E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Painful diabetic neuropathy |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012680 |
|
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 |
The primary objective of the trial is to assess the safety and tolerability of long-term SPM 927 administration in subjects with painful diabetic neuropathy. |
|
E.2.2 | Secondary objectives of the trial |
Additional objectives are to investigate the following:
1. Effect of long-term use of SPM 927 on subjects' perception of pain as measured by various assessments. 2. Effect of SPM 927 on the interference of pain on subjects' sleep and activity. 3. Effect of long-term use of SPM 927 on subjects' quality of life. 4. Effect of long-term use of SPM 927 on subjects' work productivity and activity. 5. Effect of long-term use of SPM 927 on subjects' sleepiness. 6. Effect of add-on therapy on the safety, tolerability, and efficacy of SPM 927 in subjects with painful diabetic neuropathy. 7. Effect of long-term use of SPM 927 in subjects who have not previously responded to treatment with gabapentin. 8. Subject satisfaction with SPM 927 treatment for pain due to diabetic neuropathy compared with any prior pain medications. 9. Correlation of plasma concentrations of SPM 927 with cardiac safety variables.
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
A subject is considered eligible for participation in the trial if the following inclusion criteria are satisfied at Visits 1 and 2.0: 1. Subject is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent. 2. Subject is willing and able to comply with all trial requirements, including the completion of trial questionnaires. 3. Subject is male or female, ≥18 years of age. 4. Subject has symptoms of painful diabetic neuropathy for at least 6 months and has a diagnosis of diabetes mellitus (Type I or Type II). Subjects who have had symptoms of painful diabetic neuropathy for longer than 5 years may be enrolled after consultation with the medical monitor. 5. Subject has HbA1c levels <12% with optimized diabetic control (best effort to achieve best control) for at least 3 months prior to Visit 1. 6. Subject has at least moderate pain that is defined as an average pain intensity of ≥4 on an 11 point Likert scale (0-10) during the 7 days prior to Visit 2, where at least 4 out of the 7 days have both the morning and evening scores recorded in the subject diary.
|
|
E.4 | Principal exclusion criteria |
A subject is not eligible for participation in the trial if any of the following exclusion criteria are met at Visit 1: 1. Subject has previously participated in this trial or subject has previously been assigned to treatment in a trial of the drug under investigation in this trial. 2. Subject has participated in another trial of an investigational drug (or a medical device) within the last 30 days or is currently participating in another trial of an investigational drug or medical device. 3. Subject has other conditions that cause chronic pain at least as severe as the diabetic neuropathy pain, unless subject can clearly distinguish the different types of pain. These cases should be discussed with the medical monitor. 4. Subject is expected to take within 7 days prior to Visit 2 or during the Titration Phase and Maintenance Phase A of the trial AEDs, muscle relaxants, mexiletine, topical analgesics, opioids or unstable doses of tricyclic antidepressants (TCAs). Paracetamol (acetaminophen) up to 2g/day is allowed as rescue medication during the entire trial. 5. Subject is receiving treatment with neurostimulating devices such as spinal cord stimulation (SCS) or peripheral nerve stimulation (PNS). Treatment for pain with acupuncture, surgery, or blockade is not allowed until completion of Maintenance Phase A of the trial. 6. Subject has had an amputation related to diabetes, other than toe amputations. 7. Subject has major skin ulcers. 8. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin levels ≥2 times the upper limit of normal (ULN) or has alkaline phosphatase levels ≥3 times the ULN at Visit 1. 9. Subject has impaired renal function, ie, creatinine clearance is lower than 50mL/min at Visit 1. Creatinine clearance (Ccr) will be estimated as follows: Adult males: Ccr = (140-age) x weight in kg/(72 x serum creatinine in mg/dL) Adult females: Ccr = ([140-age] x weight in kg/[72 x serum creatinine in mg/dL]) x .85. 10. Subject has other laboratory values, which are outside the normal range at Visit 1 and judged by the investigator as clinically relevant. Exceptions are out-of-range values that are expected in this diabetic population (eg, elevated glucose). 11. Subject has experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months, or has any cardiac disorder that, in the opinion of the investigator, would put the subject at risk of clinically relevant arrhythmia and/or myocardial infarction. 12. Subject has a QTc ≥470ms at Visit 1, where QTc is based on a central cardiologist overread. 13. Subject has 2° or 3° AV block or sinus bradycardia (heart rate <50 beats per minute [bpm]) or sinus tachycardia (heart rate >110bpm) at Visit 1, based on a central cardiologist overread. 14. Subject has diastolic blood pressure <50mmHg or >105mmHg, measured in a sitting position after 3 minutes at rest. 15. Subject has a history of alcohol or drug abuse within the last year. 16. Subject has any medical or psychiatric condition that, in the opinion of the investigator, would jeopardize or compromise the subject's ability to participate in this trial or could confound the analysis of efficacy. 17. Subject has known hypersensitivity to any components of the trial medication (or rescue medication) as stated in this protocol. 18. Subject is a pregnant or nursing female, or is of childbearing potential and is not surgically sterile, 2 years postmenopausal, or does not practice 2 combined methods of contraception.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Adverse events reported spontaneously by the subject or observed by the investigtor.
2. Changes in hematology, clinical chemistry, and urinanalysis parameters.
3. Changes in vital sign measurements and physical (including neurological) examination findings.
4. Changes in 12-lead ECGs.
5. Subject withdrawals due to adverse events. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |