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Efficacy Study With 500 mg QD of TRO19622 vs Placebo in Patients With Painful Peripheral Diabetic Neuropathy

Phase 2
Completed
Conditions
Diabetic Neuropathy
Interventions
Drug: Experimental
Drug: Placebo comparator
Registration Number
NCT00496457
Lead Sponsor
Hoffmann-La Roche
Brief Summary

The purpose of this study is to assess the efficacy and safety of TRO19622 administered PO daily for 6 weeks compared to placebo administered PO daily in patients with painful peripheral diabetic neuropathy.

Detailed Description

Diabetic peripheral neuropathic pain (DPNP) affects approximately 11% of patients with diabetic peripheral neuropathy (DPN). Diabetic neuropathy as the underlying disease is the most common long-term complication of diabetes mellitus estimated to be experienced by a majority of patients at least in a mild manner.

Many patients with (DPNP) do not respond adequately to any individual treatment option. None of the various treatments used can be considered a cure. As a result, although a variety of drugs are available for the treatment of diabetic neuropathic pain, there is a strong need to develop new drugs with greater efficacy and/or fewer adverse effects.

The primary objective of the study is to compare the effect of TRO19622 versus placebo on the 24h neuropathic pain scores during the last 7 days of the 6-week treatment period.

Secondary objectives are to compare the efficacy on neuropathic pain, impact on emotional functioning, safety profile, pain time course, and response rate of TRO19622 versus placebo. Additionally, the pharmacokinetics of TRO19622 will be assessed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
159
Inclusion Criteria
  • Be a male >18 years or a post-menopausal female (>60 years of age and at least 1 year of amenorrhea).
  • Have painful diabetic neuropathy of >6 months duration and are either pain treatment naive or have important side effects or inadequate relief from their current pain medication.
  • Be on current pain medication (prescribed analgesics), stable for at least 3 months before study entry (± 25% dosage of basic pain medication, top-up rescue medication allowed), or pain treatment naive.
  • Have stable diabetes, defined as HbA1c <10%, no changes in medication in the previous 3 months, and no new symptoms associated with diabetes in the previous 3 months.
  • Have scored >2 points on the Michigan Neuropathy Screening Instrument (MNSI), part B-physical assessment by health professional.
  • Have an ECG without any clinically significant abnormality.

The following inclusion criteria should be ascertained at the baseline visit:

  • Have measurable pain perception (previous 24h) on the Likert numerical rating scale with a mean≥4.0 points calculated from at least 4 daily measurements over the 7 days immediately prior to the Baseline Visit.
  • Have stopped current pain medication at least 14 days prior to the Baseline Visit (except rescue medication).
Exclusion Criteria
  • Be pregnant female, lactating female, or female of child bearing potential (≤60 years of age).

  • Have a documented neuropathy of any cause other than those mentioned in the inclusion criteria which might interfere with the assessment of the severity of pain (eg, including, but not limited to, alcoholic, uremic, B12, TSH, chemotherapy, HIV, post surgical, or post-traumatic neuropathy).

  • Have other neurological diseases that may produce weakness, sensory loss, or autonomic symptoms, or laboratory test abnormality.

  • Have been on pain treatment with strong opioids, more than 4 different drug regimens in the previous year, or a current combination of more than 2 drugs.

  • Have a current medication of lipid lowering agents other than statins.

  • Have a body mass index (BMI) >40 kg/m2 (obesity grade III).

  • Had any surgery within the previous 2 months.

  • Have concurrent serious neurological disease (eg, dementia, multiple sclerosis, or any other disease that would impact the ability of the patient to provide consent for study participation).

  • Have a recent history (within the previous 6 months) or current evidence of alcohol or drug abuse.

  • Have concurrent unstable disease involving any system (eg, advanced carcinoma, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency i.e.≥ NYHA functional classification class 2, anginal symptoms, current symptoms of CAD, renal impairment, or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation).

  • Participated in any other investigational drug or therapy study within the previous 3 months.

  • Changed or interrupted current well-tolerated medication during the previous 3 months.

  • Lack of ability or willingness to give informed consent.

  • Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).

  • Have hemostasis disorders or a current treatment of anticoagulants.

  • Have non-adequate renal and/or hepatic function as follows:

    • Renal - Blood creatinine >1.5X upper limit of normal (ULN)
    • Hepatic - Liver enzymes (ALT and AST) >2 X ULN
  • Have a known history of or current cardiac dysrhythmias and / or a known history of or current cardiovascular disease including myocardial infarction except patients with well controlled hypertension only.

  • Are not able to comply with regard to the known contraindications, warnings and precautions, drug-interactions and dosing recommendations of paracetamol.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1ExperimentalTRO19622
2Placebo comparator-
Primary Outcome Measures
NameTimeMethod
Effect of TRO19622 versus Placebo on the mean 24h neuropathic pain score on the Likert numerical rating scale.During the last 7 days of the 6-week treatment period
Secondary Outcome Measures
NameTimeMethod
24h Pain time courseDuration of study (within 11weeks after screening)
Analysis for treatment effects: SF-MPQ, SF-BPI, SF36, POMS, Global Impression of Change (Patient / Investigator)Within 6 weeks of treatment
Adverse eventsDuring the course of the study.

Trial Locations

Locations (31)

Genaral Hospital "Josip Bencevic", Internal Medicine Department-Unit for Diabetes, Andrije Stampara 42

🇭🇷

Slavonski Brod, Croatia

General Hospital Varazdin, Internal Medicine Department-Unit for Diabetes, Ivana Mestrovica bb

🇭🇷

Varazdin, Croatia

Center for Neurology, Clinical Centre "Kragujevac"

🇷🇸

Kragujevac, Serbia

Zemgale's Diabetes Centre SIA - Zemgales boulevard 15

🇱🇻

Jelgava, Latvia

Centrum Neurologii Klinicznej - Ul. Dwernickiego 8

🇵🇱

Kraków, Poland

Adamiec Rajmund Gabinet Lekarski, ul. Żelazna 34

🇵🇱

Wrocław, Poland

Centre of Neurology, Clinical Hospital Centre "Dr Dragisa Misovic"

🇷🇸

Belgrade, Serbia

Institute for Endocrinology, Clinical Centre Serbia

🇷🇸

Belgrade, Serbia

Neurology Clinic, Military Medical Academy

🇷🇸

Belgrade, Serbia

NZOZ Specjalistyczny Ośrodek, Internistyczno-Diabetologiczny, ul Zamenhofa 10/20

🇵🇱

Białystok, Poland

Neurology Department, Clinical Hospital Zemun

🇷🇸

Belgrade, Serbia

NZOZ MEDICA, ul. Jutrzenki 4

🇵🇱

Lublin, Poland

Clinic for Neurology and Psychiatry, Clinical Hospital Centre "Zvezdara"

🇷🇸

Belgrade, Serbia

Daugavpils Regional Hospital - Vasarnicu street 20

🇱🇻

Daugavpils, Latvia

Universitätsklinikum Heidelberg - Abteilung Innere Medizin I und klinische Chemie - Im Neuenheimer Feld 410

🇩🇪

Heidelberg, Germany

Univerity Hospital OSIJEK, Department for Diabetes and Endocrinology, J.Huttlera 4

🇭🇷

Osijek, Croatia

University Hospital "Dubrava", University Department for Internal Medicine, Institut for Diabetes, Endocrinology and Metabolic diseases, Avenija Gojka Suska 6

🇭🇷

Zagreb, Croatia

Diabetologische Schwerpunktpraxis - Wilhelminenstr. 22

🇩🇪

Dinslaken-Bruch, Germany

Pro scientia med - Osterweide 10

🇩🇪

Lübeck, Germany

Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH, Hebbelstr. 1A

🇩🇪

Potsdam, Germany

Doctor's Practice in Endocrinology - Meža prospekts 9, 2nd floor, 41.kabinets

🇱🇻

Ogre, Latvia

Talsu Hospital - Rugena street 7

🇱🇻

Talsi, Latvia

NZOZ Special-Med. Ul. Weteranów 46

🇵🇱

Lublin, Poland

Deutsches Diabetes Center, Institut für Klinische Diabetologie, Leibniz-Zentrum an der Heinrich-Heine Universität - Auf'm Hennekamp 65

🇩🇪

Duesseldorf, Germany

Diabetes Zentrum Mergentheim - Theodor-Klotzbücher-Straße 12

🇩🇪

Bad Mergentheim, Germany

Klinikum Region Hannover GmbH - Klinikum Hannover Nordstadt - Diabetes Schwerpunktklinik -Medizinische Klinik - Haltenhoffstr. 41

🇩🇪

Hannover, Germany

Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH - Hebbelstr. 1A

🇩🇪

Potsdam, Germany

Sophien- und Hufeland-Klinikum gGmbH - Klinik für Neurologie und Klinische Neurophysiologie - Henry-van-de-Velde-Str. 2

🇩🇪

Weimar, Germany

IKFE GmbH - Institut für klinische Forschung und Entwicklung - Parcusstr. 8

🇩🇪

Mainz, Germany

Clinical Research Centre "Riga" - Katrinas dambis 16

🇱🇻

Riga, Latvia

NZOZ Beta-Med., Plac Wolności 17

🇵🇱

Rzeszów, Poland

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