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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012680 |
E.1.2 | Term | Diabetic neuropathy |
|
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 this study is to provide evidence of the effectiveness of E2007 for treating pain associated with periperal painfulof diabetic neuropathy. (PDN) |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: • To evaluate the effects of E2007 on secondary variables, including: interference with sleep, functional status, and patient impression of change in neuropathic pain • To determine the relationship between dose (four doses of E2007 and placebo) and response (both efficacy and safety) • To study the safety and tolerability of E2007 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent, prior to entering the study or undergoing any study procedures.
2. Male and female patients ≥18 years of age will be eligible for enrollment. Females should be either not of childbearing potential as a result of surgery or menopause (one year after onset), or of childbearing potential and practicing a medically acceptable method of contraception (eg, abstinence, a barrier method plus spermicide, or intrauterine device [IUD]) for at least one month before Screening (Visit 1) and for one month after the end of the study (Visit 8). They must also have a negative serum beta-human chorionic gonadotropin (ß-hCG) at Screening (Visit 1). Those females using hormonal contraceptives must also be using an additional approved method of contraception (eg, a barrier method plus spermicide or IUD) starting with the Baseline Phase and continuing throughout the study period.
3. Have Type I or Type II diabetes with painful, distal, symmetrical, sensory-motor neuropathy attributed to diabetes, of at least 12 months duration
4. Have pain that has been stable over the past six months and, in the opinion of the investigator, not in an identifiably improving or worsening trend
5. Have hemoglobin A1c (HgA1c) ≤ 11%
6. Score of ≥-40 mm on the visual analog scale (VAS) of the SF- MPQ at both Screening (Visit 1) and Baseline (Visit 2 prior to randomization)
7. Have completed the patient diary for at least 6 of the 7 days prior to Baseline (Visit 2)
8. Have an average daily pain score of ≥ 4, on an 11-point Likert-type numeric rating scale during the seven days prior to Baseline (to be obtained from the patient diary)
9. Be reliable, willing, and able to cooperate with all study procedures including the following: a. Accurately fill out the diary on a daily basis b. Return for study visits on the required dates c. Accurately and reliably report symptoms (including treatment-emergent signs and symptoms) d. Take study drug as required by protocol
10. Be on stable antidiabetic treatment (insulin, oral agents, or lifestyle) that is not anticipated to change during the course of the study, except if medically required; a flexible insulin regimen controlled and monitored by the patient is considered stable antidiabetic treatment (revised per Amendment 01)
11. Be on stable analgesic treatment (same medication and dose) or stable nonpharmacological pain treatment for at least four weeks prior to Screening (Visit 1) and remain on this stable treatment throughout the study (unless otherwise directed by a physician). Nonpharmacologic pain treatment includes the following: Relaxation/hypnosis, physical or occupational therapy, counseling, etc. Episodic or periodic pharmacologic treatments such as monthly injections for treatment of pain (eg, local anesthetics) will not be permitted (revised per Amendment 01). |
|
E.4 | Principal exclusion criteria |
1. Any condition that could interfere with the conduct of the study or confound efficacy evaluations including the following: a. Pain or neuropathy from another cause (including central pain, radiculopathy, painful arthritis, etc.) b. Skin or soft-tissue lesions in the area affected by neuropathy that are painful or could alter sensation c. Amputation, other than toes
2. Motivation by secondary gain, or where there is a negative-incentive to achieving pain and functional pain relief (eg, litigation). This will be determined by the patient’s medical history.
3. Clinically significant, progressive, or potentially unstable disease of any body system including cardiovascular, gastrointestinal, CNS, psychiatric, endocrine (other than diabetes), or immunologic, including patients with any of the following broad disease categories: a. Systemic infections (eg, human immunodeficiency virus [HIV], hepatitis, tuberculosis [TB], syphilis); lack of appropriate medical history of these conditions is acceptable (revised per Amendment 01) b. History of past (within the past 12 months) or present drug or alcohol abuse as per the Diagnostic and Statistical Manual – 4th Edition (DSM IV) criteria c. History of acute coronary syndrome within the past 12 months d. Active cancer within the previous five years except treated basal cell carcinoma of the skin (revised per Amendment 01). e. Systemic chemotherapy or immunotherapy within the past five years f. History of major depression, bipolar disease, psychosis or suicidal ideation or attempts within the past five years
4. Any of the following laboratory abnormalities at Screening (Visit 1) or Baseline (Visit 2): a. Clinically significant ECG abnormality, including prolonged QTc (defined as QTc ≥ 450 msec) b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal (ULN) c. Clinically significant white blood cell (WBC) count or absolute neutrophil count, platelet count values (revised per Amendment 01) d. Positive urine drug screen for drugs of abuse, except those prescribed by a properly licensed practitioner (eg, opioids such as codeine for neuropathic pain) e. Other clinically significant laboratory values
5. Exposure to an investigational drug (including E2007) within the 30 days prior to Screening (Visit 1) or any prior exposure to E2007
6. Use of any medication known to be a strong inducer of CYP3A4 activity within four weeks prior to Screening (Visit 1); use of CYP3A4 inducers is prohibited for the entire study duration (revised per Amendment 01). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be a 24-hour daily pain intensity score, captured on an 11-point Likert-type numeric rating scale using a daily patient diary where 0 represents no pain and 10 represents the worst imaginable pain. Pain scores will be averaged over the last seven days prior to randomization and prior to the End of Treatment. This variable will be analyzed as change in pain score from BL to EOT. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |