E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuropathic pain in diabetic patients |
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E.1.1.1 | Medical condition in easily understood language |
Neuropathic pain is pain that comes from problems with signals from the nerves. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067547 |
E.1.2 | Term | Diabetic peripheral neuropathic pain |
E.1.2 | System Organ Class | 100000004852 |
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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 |
To assess the efficacy of 200 mg t.i.d. of PL37 + pregabalin or gabapentin compared to pregabalin or gabapentin plus placebo in the reduction of pain intensity in patients suffering from neuropathic pain of diabetic origin. |
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E.2.2 | Secondary objectives of the trial |
SECONDARY OBJECTIVES:
To assess the safety/tolerability and efficacy of 200 mg t.i.d. of PL37 + pregabalin or gabapentin compared to pregabalin or gabapentin plus placebo on:
1. Clinical and biological safety profile including occurrence of Adverse Events, the potential changes in vital signs, electrocardiogram (ECG) and biological parameters;
2. Patient and clinician ratings of improvement and treatment satisfaction (Patient Global Impression of Change [PGIC] scale and the Clinical Global Impression of Change [CGIC, respectively]);
3. Changes in the nature of the patient’s subjective assessment of neuropathic pain (DN4 Questionnaire); the DN4 is physician administered;
4. Changes in the patient’s subjective assessment of diabetic neuropathic pain (Michigan Neuropathy Screening Instrument [MNSI]); the MNSI is partially completed by subject and partially physician administered. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
1. Willing and able to provide written informed consent prior to any study related procedures
2. Male or female, aged ≥18 years and ≤75 years
3. Willing to comply with all study procedures and be available for the duration of the study
4. Diagnosed (confirmed by pain specialist or endocrinologist) with peripheral neuropathic pain of diabetic origin
5. Neuropathic pain lasting for at least 3 months
6. Mean 24-hour average pain intensity score of 4 or higher, as calculated from a minimum of 5 NRS ratings recorded by the patient over the 7 days period after the screening and prior to the randomisation visit and also between the randomisation and the dispensing visit (this eligibility criterion will be provided by IVR system/ePRO diary)
7. Stable treatment with pregabalin or gabapentin for at least one month prior to screening visit
8. Adequately controlled diabetes (HbA1c ≤10% or 86 mmol/mol)
9. Women of reproductive potential must use highly effective contraception from screening to 1 week after end of study treatment. (A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly, such as implants, injectable, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or a vasectomised partner)
10. Men of reproductive potential must use condoms from screening to 1 week after end of study treatment
11. HADS-Depression score ≤ 11
12. Stable dose of any allowed central nervous system (CNS) - acting medications for at least one month prior to screening visit |
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E.4 | Principal exclusion criteria |
1. Unstable angina, heart failure and significant pulmonary disease requiring home oxygen
2. Severe renal disease defined as eGFR < 30 mL/min/1,73m2 calculated by using either the CKD-EPI or MDRD equation
3. Liver disease or any liver function test > 2.5 x ULN
4. Other painful medical conditions that could interfere with assessment of study outcomes (rheumatoid arthritis, inflammatory bowel disease, mechanical lower back disorders)
5. Use of disallowed concomitant medications (systemic analgesic, opioids or anti-inflammatory medications [other than paracetamol] or capsaicin cream during two weeks prior to screening visit)
6. Recent (last 2 weeks) febrile illness that precludes or delays participation
7. Inability to swallow study medication
8. Pregnant females as determined by positive urine pregnancy at randomisation visit
9. Breastfeeding females
10. Known hypersensitivity or intolerance to components of the study product(s)
11. Treatment with another investigational drug or other intervention during the last 4 weeks prior to screening visit
12. History of drug/alcohol abuse
13. History of severe psychiatric disorder
14. Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject’s full compliance with or completion of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in weekly mean of the 24-hour average pain intensity, self-assessed using the NRS for pain, from baseline to end of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to end of treatment. |
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E.5.2 | Secondary end point(s) |
Efficacy: change from baseline in DN4 scores and MNSI scores, PGIC and CGIC response rates.
Safety: incidence of adverse events, change from baseline in vital signs, change from baseline in ECG parameters, change from baseline in laboratory parameters. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
DN4 - Visits 2 and 5
MNSI - Visits 2 and 5
PGIC - Visit 5
CGIC - Visit 5
Safety: throughout the study |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |