E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Painful distal 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 investigate the efficacy of 400mg/day of LCM compared with placebo in reducing pain in subjects with painful distal diabetic neuropathy. Two titration schemes will be used; the first is a standard titration scheme such that the target dose of 400mg/day is attained at Day 22, the second is a more rapid titration scheme and the target dose of 400mg/day is attained at Day 8. Each titration scheme will be compared with placebo. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to investigate the onset of action under treatment of LCM, the effect of LCM on subjects’ perception of pain, sleep, activity, and quality of life, and to further investigate the safety of LCM. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must fulfill the following inclusion criteria:
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.
3. Subject is male or female, >=18 years of age.
4. Subject has had 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 only be enrolled after consultation with the Medical Monitor.
5. Subject has good to fair diabetic control (glycosylated hemoglobin A1c [HbA1c] levels <12%), which is optimized (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.
|
|
E.4 | Principal exclusion criteria |
Subjects are not permitted to enroll in the trial if any of the following criteria are met:
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 randomization or during the trial AEDs, muscle relaxants, mexiletine, topical analgesics, opioids or unstable doses of tricyclic antidepressants (TCAs), or any other approved therapy for treating painful diabetic neuropathy (such as duloxetine). Paracetamol 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 not allowed.
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 (Ccr) is lower than 50mL/min at Visit 1. Creatinine clearance 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 within the last 12 months.
12. Subject has a QTc >=470ms at Visit 1, where QTc is based on a central cardiologist overread.
13. Subject has 2° or 3° atrioventricular 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 <50mm Hg or >105mm Hg, 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 scheduled or expects to schedule a surgical procedure during the course of the trial.
17. 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.
18. Subject has known hypersensitivity to any components of the trial medication (or rescue medication) as stated in this protocol.
19. Subject is a pregnant or nursing female, or is of childbearing potential and does not practice adequate methods of contraception (eg, implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or vasectomized partner). Women who are surgically sterile (uterus removed or both tubes tied) or postmenopausal (at least 2 years without periods) are allowed to participate in this trial.
20. Subject has sick sinus syndrome and does not have a pacemaker.
21. Subject has atrial fibrillation/flutter, ventricular tachyarrhythmia (eg, ventricular tachycardia, ventricular fibrillation, aborted cardiac arrest), symptomatic heart block at Visit 1, or is diagnosed with Brugada syndrome.
22. Subject has diagnosis of New York Heart Association Class III or Class IV heart failure.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the within-subject change in average daily pain score from the Baseline week to the last 4 weeks of the Maintenance Phase using an 11-point Likert scale (0-10). |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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
|
The end of the trial is defined as the date of 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 | 0 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |