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

Diabetic Neuropathy Clinical Trial

Official title:

A Double-Blind, Randomized, Multicenter Study With 500 mg QD of TRO19622 Versus Placebo in Patients With Painful Peripheral Diabetic Neuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00496457
• Other study ID #: WN29860
• Secondary ID: EudraCT Number:
• Status: Completed
• Phase: Phase 2
• First received: June 22, 2007
• Last updated: November 21, 2016
• Start date: May 2007
• Est. completion date: December 2008

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSerbia: Local Ethic CommitteesCroatia: Ministry of Health and Social CareLatvia: State Agency of MedicinesPoland: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• Experimental
Capsules of TRO19622 (125 mg)- Once a day before noon meal during 6 weeks
• Placebo comparator
4 Capsules of PBO per day before noon meal

Locations

Country	Name	City	State
Croatia	Univerity Hospital OSIJEK, Department for Diabetes and Endocrinology, J.Huttlera 4	Osijek
Croatia	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	University Hospital "Dubrava", University Department for Internal Medicine, Institut for Diabetes, Endocrinology and Metabolic diseases, Avenija Gojka Suska 6	Zagreb
Germany	Diabetes Zentrum Mergentheim - Theodor-Klotzbücher-Straße 12	Bad Mergentheim
Germany	Diabetologische Schwerpunktpraxis - Wilhelminenstr. 22	Dinslaken-Bruch
Germany	Deutsches Diabetes Center, Institut für Klinische Diabetologie, Leibniz-Zentrum an der Heinrich-Heine Universität - Auf'm Hennekamp 65	Duesseldorf
Germany	Klinikum Region Hannover GmbH - Klinikum Hannover Nordstadt - Diabetes Schwerpunktklinik -Medizinische Klinik - Haltenhoffstr. 41	Hannover
Germany	Universitätsklinikum Heidelberg - Abteilung Innere Medizin I und klinische Chemie - Im Neuenheimer Feld 410	Heidelberg
Germany	Pro scientia med - Osterweide 10	Lübeck
Germany	IKFE GmbH - Institut für klinische Forschung und Entwicklung - Parcusstr. 8	Mainz
Germany	Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH - Hebbelstr. 1A	Potsdam
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
Latvia	Daugavpils Regional Hospital - Vasarnicu street 20	Daugavpils
Latvia	Zemgale's Diabetes Centre SIA - Zemgales boulevard 15	Jelgava
Latvia	Doctor's Practice in Endocrinology - Meža prospekts 9, 2nd floor, 41.kabinets	Ogre
Latvia	Clinical Research Centre "Riga" - Katrinas dambis 16	Riga
Latvia	Talsu Hospital - Rugena street 7	Talsi
Poland	NZOZ Specjalistyczny Osrodek, Internistyczno-Diabetologiczny, ul Zamenhofa 10/20	Bialystok
Poland	Centrum Neurologii Klinicznej - Ul. Dwernickiego 8	Kraków
Poland	NZOZ MEDICA, ul. Jutrzenki 4	Lublin
Poland	NZOZ Special-Med. Ul. Weteranów 46	Lublin
Poland	NZOZ Beta-Med., Plac Wolnosci 17	Rzeszów
Poland	Adamiec Rajmund Gabinet Lekarski, ul. Zelazna 34	Wroclaw
Serbia	Centre of Neurology, Clinical Hospital Centre "Dr Dragisa Misovic"	Belgrade
Serbia	Clinic for Neurology and Psychiatry, Clinical Hospital Centre "Zvezdara"	Belgrade
Serbia	Institute for Endocrinology, Clinical Centre Serbia	Belgrade
Serbia	Neurology Clinic, Military Medical Academy	Belgrade
Serbia	Neurology Department, Clinical Hospital Zemun	Belgrade
Serbia	Center for Neurology, Clinical Centre "Kragujevac"	Kragujevac

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Ergomed GmbH

Countries where clinical trial is conducted

Croatia,  Germany,  Latvia,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	24h Pain time course		Duration of study (within 11weeks after screening)	Yes
Secondary	Analysis for treatment effects: SF-MPQ, SF-BPI, SF36, POMS, Global Impression of Change (Patient / Investigator)		Within 6 weeks of treatment	Yes
Secondary	Adverse events		During the course of the study.	Yes