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Painful Diabetic NeuropathyPhase 2NCT03749642

Trazodone/Gabapentin Fixed Dose Combination Products in Painful Diabetic Neuropathy

A Phase 2 study testing trazodone/gabapentin 2.5/25 mg, trazodone/gabapentin 5/50 mg and trazodone/gabapentin 10/100 in people with Painful Diabetic Neuropathy, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 30 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of the study is to collect preliminary information on the effect of three doses of trazodone/gabapentin FDC products on pain intensity in patients with painful diabetic neuropathy after 8-week treatment period. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Painful Diabetic Neuropathy
What is being tested?
trazodone/gabapentin 2.5/25 mg, trazodone/gabapentin 5/50 mg and trazodone/gabapentin 10/100
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
240 participants
Where
30 sitesin 4 countries
Study dates
22 Nov 2018to 6 Jun 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female patient of any ethnic origin between 18 and 75 years of age (limits included).
  • Neuropathic pain at feet/legs confirmed by Douleur Neuropatique 4 (DN4) score ≥ 4 at Screening Visit.
  • Patient with bilateral distal symmetrical polyneuropathy confirmed by Toronto Clinical Neuropathy Scoring System (TCNSS) score > 5 at Screening visit.
  • Pain persisting or taking pain medication for neuropathic pain for at least 3 months.
  • Diabetic patient (type 1 or 2 diabetes mellitus) with value of glycated haemoglobin ≤ 11% at Screening Visit and stable antidiabetic medication regimen for ≥30 days.
  • 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.
Show all 9Show fewer
  • 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.
  • 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.
  • 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.

Who cannot join

  • Known hypersensitivity to trazodone or gabapentin or any excipients of the test drugs.
  • 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).
  • Concomitant treatment with medications for pain management that could not be discontinued.
  • Concomitant treatment with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir) or drugs known to prolong QT interval.
  • Use of trazodone or gabapentin in the previous 3 months.
  • Known history of previous non-responder to gabapentin treatment.
Show all 27Show fewer
  • Use of high dose morphine (e.g. > 120 mg/day) at the Screening Visit.
  • Clinically significant abnormalities on physical examination, vital signs, elettrocardiogram, laboratory tests at Screening Visit that in the opinion of Investigator would compromise patient's participation in the study.
  • Active foot ulcer or previous major limb amputation.
  • 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.
  • 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.
  • Transient ischemic attack or cerebral vascular accident within the past 6 months.
  • Glomerular Filtration Rate value < 50 ml/min calculated with Modification of Diet in Renal Disease formula.
  • Significant liver disease, defined as known active hepatitis or elevated liver enzymes over 3-fold the upper normal limit of laboratory normal ranges.
  • Patient with latent or known hereditary problems of galactose intolerance or the Lapp lactase deficiency or glucose-galactose malabsorption.
  • Positive urine drug screen for Central Nervous System active drugs (cocaine, opioids, amphetamines and cannabinoids) at Screening Visit.
  • Positive present history of glaucoma.
  • Hyperthyroidism, even if pharmacologically corrected.
  • Significant mental disorders.
  • Suicide risk score ≥ 2 on question 9 of the Beck Depression Inventory-II (BDI-II) at Screening visit or Visit 0.
  • History of epilepsy or seizure events other than a single childhood febrile seizure.
  • History of alcohol or psychoactive substance abuse or addiction.
  • Use of neurological device (e.g. neurostimulation devices, etc).
  • Women during pregnancy or lactation period.
  • 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).
  • Subject involved in the conduct of the study (e.g. Investigator or his/her deputy, first grade relatives, pharmacist, assistant or other personnel, etc).
  • Participation to an interventional clinical trial within 3 months prior to Screening Visit.

Trial locations and contacts

30 sites in 4 countries.

30 sites in 4 countries

Poland13 sites

  • Centrum Badań Klinicznych PI-House

    Gdansk, 80-546

  • Silmedic Sp. z o.o.

    Katowice, 40-282

  • Pro Familia Altera Poradnia Wielospecjalistyczna

    Katowice, 40-648

  • Medyczne Centrum Diabetologiczno-Endokrynologiczno-Metaboliczne DIAB-ENDO-MET

    Kraków, 31-261

  • NZOZ Neuromed M. i M. Nastaj Sp. P.

    Lublin, 20-064

  • Instytut Medycyny Wsi im. Witolda Chodźki Klinika Diabetologii

    Lublin, 20-090

  • Centrum Medyczne HCP Sp. z o.o.

    Poznań, 61-485

  • RCMed Oddział Sochaczew

    Sochaczew, 96-500

  • Nasz Lekarz Przychodnie Medyczne

    Toruń, 87-100

  • Medycyna Kliniczna

    Warszawa, 00-874

  • Instytut Diabetologii

    Warszawa, 04-736

  • WroMedica I. Bielicka, A. Strzałkowska s.c.

    Wrocław, 51- 685

  • Centrum Badań Klinicznych Ośrodek Badań Wczesnej Fazy

    Wrocław, 51-162

Other trials in Poland

Czechia7 sites

  • Neurosanatio s.r.o.

    Litomyšl, 570 01

  • Cerebrovaskulární poradna, s.r.o.

    Ostrava - Poruba, 70800

  • Nemocnice Pardubického kraje a.s. Pardubická nemocnice Neurologická klinika

    Pardubice, 532 03

  • Diabetologická ambulance Milan Kvapil s.r.o.

    Praha 4, 149 00

  • Axon Clinical s.r.o

    Praha 5, 15000

  • FORBELI s.r.o.

    Praha 6, 160 00

  • Clintrial s.r.o.

    Praha, 100 00

Other trials in Czechia

United Kingdom6 sites

  • Medical Innovation Development and Research Unit (MIDRU) Heartlands Hospital

    Birmingham

  • Diabetes Centre Wythenshawe Hospital

    Manchester

  • Manchester Clinical Research Facility Manchester Royal Infirmary

    Manchester

  • Diabetes Centre George Eliot Hospital NHS Trust

    Nuneaton

  • Lancashire Clinical Research Facility The Avondale Unit Royal Preston Hospital

    Preston

  • Clinical Research Facility Royal Hallamshire Hospital

    Sheffield

Other trials in United Kingdom

France4 sites

  • Fondation Hôtel Dieu Groupe SOS Service de Diabétologie

    Le Creusot

  • GHR MSA - Hôpital Emile Muller Service de Diabétologie-Endocrinologie-Nutrition

    Mulhouse

  • CHU de Nantes - Hôpital Guillaume-et-René-Laënnec Clinique d'Endocrinologie, maladies métaboliques et nutrition CIC Endocrino - Nutrition - UF 7015

    Nantes Cedex 144 093

  • Centre de Recherche Clinique G.H.M les Portes du Sud Departement d'Endocrinologie

    Vénissieux

Other trials in France

About this study

Official title: Efficacy and Safety of Fixed-Dose Combination (FDC) Products Containing Trazodone and Gabapentin in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose Finding Study.

The primary objective of the study is to collect preliminary information on the effect of three doses of trazodone/gabapentin FDC products on pain intensity in patients with painful diabetic neuropathy after 8-week treatment period.

Read the detailed description

The present phase II study is designed to collect preliminary data on the efficacy and safety of trazodone/gabapentin Fixed-Dose Combination (FDC)products for treatment of patients affected by painful diabetic neuropathy in a randomized controlled clinical trial. Diabetic peripheral neuropathic pain represents an important therapeutic challenge as its pathophysiology is not yet fully understood and pain relief is still unsatisfactory. The pharmacological treatments, with exception to those targeted to the glycemic control, are symptomatic and their use is limited by not universal efficacy, side effects or by the development of tolerance. A wide variety of drugs, used both alone and in combination, has shown to significantly reduce neuropathic pain when compared with placebo in randomized controlled trials, even though pain relief remains inadequate for most of the patients.

In this contest, Angelini S.p.A is developing a fixed-dose combination medicinal product for the treatment of neuropathic pain containing low doses of active ingredients: trazodone, a widely used antidepressant drug, and gabapentin which is indicated for the treatment of neuropathic pain.

Being tested
trazodone/gabapentin 2.5/25 mg, trazodone/gabapentin 5/50 mg, trazodone/gabapentin 10/100, Gabapentin, Placebo oral capsule
Keywords
Trazodone, Gabapentin, Neuropathic pain, Placebo
Medical subject headings
Diabetic Neuropathies, Neuralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • trazodone/gabapentin 2.5/25 mgDrug

    The total daily doses administered will be trazodone 7,5 mg and gabapentin 75 mg.

  • trazodone/gabapentin 5/50 mgDrug

    The total daily doses administered will be trazodone 15 mg and gabapentin 150 mg.

  • trazodone/gabapentin 10/100Drug

    The total daily doses administered will be trazodone 30 mg and gabapentin 300 mg.

  • GabapentinDrug

    Also called Neurontin

    The total daily doses administered will be:

    • 600 mg from day 0 to day 6 (±1)
    • 900 mg from day 7 (±1) to day 13 (±1)
    • 1200 mg from day 14 (±1) to day 20 (±1)
    • 1800 mg from day 21 (±1) to day 56 (±2)

  • Placebo oral capsuleDrug

    Two capsules, three times a day, for 8 weeks.

Study groups in NCT03749642
Study groupRoleWhat they receive
trazodone/gabapentin 2.5/25 mgExperimentalOne capsule, three times a day, for 8 weeks. The total daily doses administered will be trazodone 7,5 mg and gabapentin 75 mg.
Receives: Drug: trazodone/gabapentin 2.5/25 mg
trazodone/gabapentin 5/50 mgExperimentalOne capsule, three times a day, for 8 weeks.
Receives: Drug: trazodone/gabapentin 5/50 mg
trazodone/gabapentin 10/100 mgExperimentalOne capsule, three times a day, for 8 weeks.
Receives: Drug: trazodone/gabapentin 10/100
placeboPlacebo comparatorTwo capsules, three times a day, for 8 weeks.
Receives: Drug: Placebo oral capsule
GabapentinActive comparatoraccording to the following scheduling dosage regimen: * 100 mg (2 capsules) 3 times a day, from day 0 to day 6 (±1); * 300 mg (1 capsule) 3 times a day, from day 7 (±1) to day 13 (±1); * 400 mg (1 capsule) 3 times a day, from day 14 (±1) to day 20 (±1); * 300 mg (2 capsules) 3 times a day, from day 21 (±1) to day 55 (±2).
Receives: Drug: Gabapentin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of the average daily pain score based on the 11-point Numeric Rating Scale (NRS).

    The NRS is based on a 11-point from 0 for [no pain] to 10 [worst possible pain].

    Measured: Baseline - Day 56

Secondary outcomes (11)

  1. Change of the average daily pain score based on the 11-point Numeric Rating Scale (NRS).

    The NRS is based on a 11-point from 0 for [no pain] to 10 [worst possible pain].

    Measured: Baseline - Days 7, 14, 21, 28, 42

  2. Percentage of responder patients

    Responder patients are defined as ≥30% and ≥50% reduction from baseline of the average daily pain score based on the 11-point NRS.

    Measured: Baseline - Day 56

  3. Change of the average daily pain score based on the 11-point NRS between gabapentin and placebo as assay sensitivity.

    The NRS is based on a 11-point from 0 for [no pain] to 10 [worst possible pain].

    Measured: Baseline - Day 56

  4. Change of Brief Pain Inventory Short Form (BPI-SF) items 3, 4, 5, 6, 8 and 9 score.

    The BPI-SF is a numeric rating scale that assesses the severity of pain, its impact on daily functioning and other aspects of pain (e.g. location of pain, relief from medications). Items use a 0-10 numeric rating scale anchored at zero for "no pain" and 10 for "pain as bad as you can imagine" for Severity, and "does not interfere" to "completely interferes" for Interference.

    Measured: Baseline - Days 28, 56

  5. Change of Neuropathic Pain Symptom Inventory (NPSI) total score.

    The NPSI is a self-questionnaire specifically designed to evaluate the different symptoms of neuropathic pain: It includes 10 descriptors plus two temporal items that allow discrimination and quantification of five distinct clinically relevant dimensions of neuropathic pain syndromes.

    Measured: Baseline - Days 28, 56

  6. Change of Beck Depression Inventory - Second Edition (BDI-II)

    The BDI-II consists of 21 items to assess the intensity of depression in clinical and normal patients. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression and scored from 0 to 3.

    Measured: Baseline - Days 28, 56

  7. Change of Hospital Anxiety and Depression Scale (HADS).

    The HADS is used to assess the level of anxiety and depression that a patient is experiencing. This is 14-item scale: seven related to the anxiety and seven to depression. Each item is scored from 0 to 3.

    Measured: Baseline - Days 28, 56

  8. Change of Insomnia Severity Index (ISI).

    The ISI is a 7-item self-reported instrument measuring the patient's perception of his/her insomnia.Total score ranges from 0-28 and the following categorization is applicable: 0-7 = absence of insomnia; 8-14 = subthreshold insomnia; 15-21 = moderate insomnia; 22-28 = severe insomnia.

    Measured: Baseline - Days 28, 56

  9. Change of Euroqol-5D-5L (EQ-5D-5L)

    The EQ-5D-5L consists of the EQ-5D descriptive system (five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression assessed as no problems, slight problems, moderate problems, severe problems and extreme problems) and the EQ visual analogue scale (where the patient self-rates his/her health on a vertical visual analogue scale from 'The best health you can imagine' to 'The worst health you can imagine').

    Measured: Baseline - Days 28, 56

  10. Clinical Global Improvement or Change (CGI-C).

    CGI-C provides a global rating of patient's Improvement and scores range from "0 - not assessed" through to "7 - very much worse".

    Measured: Baseline - Days 28, 56

  11. Frequency of adverse events

    Monitoring of the treatment related adverse events.

    Measured: 65 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2018
  2. Study start22 Nov 2018
  3. Primary completion6 Jun 2020
  4. Study completion6 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, double-blind, placebo and reference controlled, placebo unbalanced, double-dummy, dose finding, parallel group, multicentre, international, prospective study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
240 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03749642
Sponsor's protocol ID
039(1)PO16357
Other IDs
2018-000133-12, 2018
Status last verified
May 2021
First submitted
20 Nov 2018
Last updated
27 May 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tesfaye S, Saravanan P, Ehler E, Zinek K, Palka-Kisielowska I, Nastaj M, Serusclat P, Lipone P, Vergallo A, Quarchioni E, Calisti F, Comandini A, Cattaneo A. Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study. Pain Ther. 2024 Aug;13(4):987-1006. doi: 10.1007/s40122-024-00624-3. Epub 2024 Jun 24.

    PubMed 38914876

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing trazodone/gabapentin 2.5/25 mg, trazodone/gabapentin 5/50 mg and trazodone/gabapentin 10/100 in people with Painful Diabetic Neuropathy, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 30 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Poland, Czechia, United Kingdom, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of the average daily pain score based on the 11-point Numeric Rating Scale (NRS). (time frame: Baseline - Day 56). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03749642, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2021.

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