Clinical trial NCT00496457: Efficacy Study With 500 mg QD of TRO19622 vs Placebo in Patients With Painful Peripheral Diabetic Neuropathy
Official title: A Double-Blind, Randomized, Multicenter Study With 500 mg QD of TRO19622 Versus Placebo in Patients With Painful Peripheral Diabetic Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Neuropathy
Keywords: Diabetic Neuropathy
Painful Peripheral Diabetic Neuropathy
TRO19622
Trophos
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Ergomed GmbH
First posted: 2007-07-04
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effect of TRO19622 versus Placebo on the mean 24h neuropathic pain score on the Likert numerical rating scale.
timeFrame: During the last 7 days of the 6-week treatment period
Secondary outcomes:
measure: 24h Pain time course
timeFrame: Duration of study (within 11weeks after screening)
measure: Analysis for treatment effects: SF-MPQ, SF-BPI, SF36, POMS, Global Impression of Change (Patient / Investigator)
timeFrame: Within 6 weeks of treatment
measure: Adverse events
timeFrame: During the course of the study.
Other outcomes:
Locations:
city: Osijek
country: Croatia
facility: Univerity Hospital OSIJEK, Department for Diabetes and Endocrinology, J.Huttlera 4
city: Slavonski Brod
country: Croatia
facility: Genaral Hospital "Josip Bencevic", Internal Medicine Department-Unit for Diabetes, Andrije Stampara 42
city: Varazdin
country: Croatia
facility: General Hospital Varazdin, Internal Medicine Department-Unit for Diabetes, Ivana Mestrovica bb
city: Zagreb
country: Croatia
facility: University Hospital "Dubrava", University Department for Internal Medicine, Institut for Diabetes, Endocrinology and Metabolic diseases, Avenija Gojka Suska 6
city: Bad Mergentheim
country: Germany
facility: Diabetes Zentrum Mergentheim - Theodor-Klotzbücher-Straße 12
city: Dinslaken-Bruch
country: Germany
facility: Diabetologische Schwerpunktpraxis - Wilhelminenstr. 22
city: Duesseldorf
country: Germany
facility: Deutsches Diabetes Center, Institut für Klinische Diabetologie, Leibniz-Zentrum an der Heinrich-Heine Universität - Auf'm Hennekamp 65
city: Hannover
country: Germany
facility: Klinikum Region Hannover GmbH - Klinikum Hannover Nordstadt - Diabetes Schwerpunktklinik -Medizinische Klinik - Haltenhoffstr. 41
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg - Abteilung Innere Medizin I und klinische Chemie - Im Neuenheimer Feld 410
city: Lübeck
country: Germany
facility: Pro scientia med - Osterweide 10
city: Mainz
country: Germany
facility: IKFE GmbH - Institut für klinische Forschung und Entwicklung - Parcusstr. 8
city: Potsdam
country: Germany
facility: Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH - Hebbelstr. 1A
city: Potsdam
country: Germany
facility: Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH, Hebbelstr. 1A
city: Weimar
country: Germany
facility: Sophien- und Hufeland-Klinikum gGmbH - Klinik für Neurologie und Klinische Neurophysiologie - Henry-van-de-Velde-Str. 2
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital - Vasarnicu street 20
city: Jelgava
country: Latvia
facility: Zemgale's Diabetes Centre SIA - Zemgales boulevard 15
city: Ogre
country: Latvia
facility: Doctor's Practice in Endocrinology - Meža prospekts 9, 2nd floor, 41.kabinets
city: Riga
country: Latvia
facility: Clinical Research Centre "Riga" - Katrinas dambis 16
city: Talsi
country: Latvia
facility: Talsu Hospital - Rugena street 7
city: Białystok
country: Poland
facility: NZOZ Specjalistyczny Ośrodek, Internistyczno-Diabetologiczny, ul Zamenhofa 10/20
city: Kraków
country: Poland
facility: Centrum Neurologii Klinicznej - Ul. Dwernickiego 8
city: Lublin
country: Poland
facility: NZOZ Special-Med. Ul. Weteranów 46
city: Lublin
country: Poland
facility: NZOZ MEDICA, ul. Jutrzenki 4
city: Rzeszów
country: Poland
facility: NZOZ Beta-Med., Plac Wolności 17
city: Wrocław
country: Poland
facility: Adamiec Rajmund Gabinet Lekarski, ul. Żelazna 34
city: Belgrade
country: Serbia
facility: Centre of Neurology, Clinical Hospital Centre "Dr Dragisa Misovic"
city: Belgrade
country: Serbia
facility: Clinic for Neurology and Psychiatry, Clinical Hospital Centre "Zvezdara"
city: Belgrade
country: Serbia
facility: Institute for Endocrinology, Clinical Centre Serbia
city: Belgrade
country: Serbia
facility: Neurology Clinic, Military Medical Academy
city: Belgrade
country: Serbia
facility: Neurology Department, Clinical Hospital Zemun
city: Kragujevac
country: Serbia
facility: Center for Neurology, Clinical Centre "Kragujevac"
Study officials:
affiliation: Trophos, Parc Scientifique de Luminy - Case 931, Luminy Biotech Enterprises, 13288 Marseille Cedex9 - France
name: Jean-Louis Abitbol, MD
role: STUDY_CHAIR
affiliation: German Diabetes Center, German Diabetes Clinic, Leibniz Institute at the Heinrich-Heine University, Auf ´m Hennekamp 65, 40225 Dusseldorf, Germany
name: Dan Ziegler, MD
role: PRINCIPAL_INVESTIGATOR
References: