Efficacy and safety of products containing trazodone and gabapentin in patients affected by painful diabeticneuropathy.

Phase 1

• Conditions: Painful diabetic neuropathy; MedDRA version: 20.0Level: LLTClassification code 10012683Term: Diabetic peripheral neuropathySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: PTClassification code 10012680Term: Diabetic neuropathySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: SOCClassification code 10014698Term: Endocrine disordersSystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2018-000133-12-CZ
• Lead Sponsor: Angelini S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-06-01
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Male and female patient of any ethnic origin between 18 and 75 years of age (limits included).
2. Neuropathic pain at feet/legs confirmed by DN4 score = 4 at Screening Visit.
3. Patient with bilateral distal symmetrical polyneuropathy confirmed by Toronto Clinical Neuropathy Scoring System (TCNSS) score > 5 at Screening visit.
4. Pain persisting or taking pain medication for neuropathic pain for at least 3 months.
5. Diabetic patient (type 1 or 2 diabetes mellitus) with value of HbA1c = 11% at Screening Visit and stable antidiabetic medication regimen for =30 days.
6. Patient who is currently not receiving treatment for diabetic neuropathic pain or patient who is receiving treatment, with drug/s other than gabapentin, and has completed the required washout.
7. Average daily pain score = 4 based on the 11-point Numeric Rating Scale (NRS) at Visit 0, calculated from a minimum of four pain ratings in daily electronic device entries during the baseline period.
8. Women of childbearing potential must have a negative pregnancy test at Screening Visit and have to agree not to start a pregnancy from the signature of the informed consent up to thirty days after the last administration of the investigational product, using an appropriate birth control method, such as combined estrogen and progestogen containing hormonal contraception (e.g. oral, intravaginal, transdermal), progestogen-only hormonal contraception (e.g. oral, injectable, implantable), intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) in combination with male condom, bilateral tubal occlusion, vasectomised partner, sexual abstinence.
9. Legally capable to give their consent to participate in the study (including personal data processing) and available to sign and date the written informed consent.
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1. Known hypersensitivity to trazodone or gabapentin or any excipients of the test drugs.
2. Any other form of non-diabetic distal symmetric polyneuropathy or any other pain condition that can impair the study endpoint (e.g. painful conditions where the intensity of pain is significantly more severe than the diabetic peripheral neuropathic pain).
3. Concomitant treatment with medications for pain management that could not be discontinued.
4. Concomitant treatment with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir) or drugs known to prolong QT interval.
5. Use of trazodone or gabapentin in the previous 3 months.
6. Known history of previous non-responder to gabapentin treatment.
7. Use of high dose morphine (e.g. > 120 mg/day) at the Screening Visit.
8. Clinically significant abnormalities on physical examination, vital signs, ECG, laboratory tests at Screening Visit that in the opinion of Investigator would compromise patient’s participation in the study.
9. Active foot ulcer or previous major limb amputation.
10. Concurrent heart failure = 4 class according to New York Heart Association (NYHA) or myocardial infarction or angioplasty or by-pass graft procedures within the past 6 months.
11. Patient with increased risk of Torsade de Pointes (e.g. family history of long QT syndrome) or QTcF value higher than 450 msec (male) and QTcF value higher than 470 msec (female) at Screening Visit.
12. Transient ischemic attack or cerebral vascular accident within the past 6 months.
13. GFR value < 50 ml/min calculated with MDRD formula.
14. Significant liver disease, defined as known active hepatitis or elevated liver enzymes (such as ALT, AST, or ?-GT) over 3-fold the upper normal limit of laboratory normal ranges.
15. Patient with latent or known hereditary problems of galactose intolerance or the Lapp lactase deficiency or glucose-galactose malabsorption.
16. Positive urine drug screen for CNS active drugs (cocaine, opioids, amphetamines and cannabinoids) at Screening Visit.
17. Positive present history of glaucoma.
18. Hyperthyroidism, even if pharmacologically corrected.
19. Significant mental disorders.
20. Suicide risk score = 2 on question 9 of the Beck Depression Inventory-II (BDI-II) at Screening visit or Visit 0.
21. History of epilepsy or seizure events other than a single childhood febrile seizure.
22. History of alcohol or psychoactive substance abuse or addiction.
23. Use of neurological device (e.g. neurostimulation device, etc).
24. Women during pregnancy or lactation period.
25. Inability to comply with the protocol requirements, instructions or study-related restrictions (e.g. uncooperative attitude, inability to return for study visits, improbability of completing the clinical study, etc).
26. Subject involved in the conduct of the study (e.g. Investigator or his/her deputy, first grade relatives, pharmacist, assistant or other personnel, etc).
27. Participation to an interventional clinical trial within 3 months prior to Screening Visit.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To collect preliminary information on the effect of three doses of trazodone/ gabapentin PDC products on pain intensity in patients with painful diabetic neuropathy after 8-week treatment period;Secondary Objective: To evaluate the percentage of responders, the change in neuropathic pain symptoms, anxiety, sleep, quality of life, and safety and tolerability;Primary end point(s): Change from baseline of the average daily pain score based on the 11-point NRS to Visit 6 (Day 56 ±2). At the end-point time, scores will be averaged from the last seven on-treatment entries in subjects’ daily electronic device, calculated from a minimum of four pain ratings in daily electronic device entries.;Timepoint(s) of evaluation of this end point: from baseline to Visit 6 (Day 56 ±2)