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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT00496457

Collaborator

Ergomed GmbH (Industry)

159

Enrollment

Locations

Arms

19.1

Duration (Months)

5.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Neuropathy	Drug: Experimental Drug: Placebo comparator	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

159 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 TRO19622	Drug: Experimental Capsules of TRO19622 (125 mg)- Once a day before noon meal during 6 weeks
Placebo Comparator: 2	Drug: Placebo comparator 4 Capsules of PBO per day before noon meal

Arm

Intervention/Treatment

Experimental: 1

TRO19622

Drug: Experimental

Capsules of TRO19622 (125 mg)- Once a day before noon meal during 6 weeks

Placebo Comparator: 2

Drug: Placebo comparator

4 Capsules of PBO per day before noon meal

Outcome Measures

Primary Outcome Measures

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

24h Pain time course [Duration 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 events [During the course of the study.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Univerity Hospital OSIJEK, Department for Diabetes and Endocrinology, J.Huttlera 4	Osijek	Croatia	31 000
2	Genaral Hospital "Josip Bencevic", Internal Medicine Department-Unit for Diabetes, Andrije Stampara 42	Slavonski Brod	Croatia	35 000
3	General Hospital Varazdin, Internal Medicine Department-Unit for Diabetes, Ivana Mestrovica bb	Varazdin	Croatia	42 000
4	University Hospital "Dubrava", University Department for Internal Medicine, Institut for Diabetes, Endocrinology and Metabolic diseases, Avenija Gojka Suska 6	Zagreb	Croatia	10 000
5	Diabetes Zentrum Mergentheim - Theodor-Klotzbücher-Straße 12	Bad Mergentheim	Germany	97980
6	Diabetologische Schwerpunktpraxis - Wilhelminenstr. 22	Dinslaken-Bruch	Germany	46537
7	Deutsches Diabetes Center, Institut für Klinische Diabetologie, Leibniz-Zentrum an der Heinrich-Heine Universität - Auf'm Hennekamp 65	Duesseldorf	Germany	40225
8	Klinikum Region Hannover GmbH - Klinikum Hannover Nordstadt - Diabetes Schwerpunktklinik -Medizinische Klinik - Haltenhoffstr. 41	Hannover	Germany	30167
9	Universitätsklinikum Heidelberg - Abteilung Innere Medizin I und klinische Chemie - Im Neuenheimer Feld 410	Heidelberg	Germany	69120
10	Pro scientia med - Osterweide 10	Lübeck	Germany	23562
11	IKFE GmbH - Institut für klinische Forschung und Entwicklung - Parcusstr. 8	Mainz	Germany	55116
12	Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH - Hebbelstr. 1A	Potsdam	Germany	14467
13	Diabetes Schwerpunktpraxis - Gesundheitszentrum Potsdam GmbH, Hebbelstr. 1A	Potsdam	Germany	14467
14	Sophien- und Hufeland-Klinikum gGmbH - Klinik für Neurologie und Klinische Neurophysiologie - Henry-van-de-Velde-Str. 2	Weimar	Germany	99425
15	Daugavpils Regional Hospital - Vasarnicu street 20	Daugavpils	Latvia	LV-5420
16	Zemgale's Diabetes Centre SIA - Zemgales boulevard 15	Jelgava	Latvia	LV-3000
17	Doctor's Practice in Endocrinology - Meža prospekts 9, 2nd floor, 41.kabinets	Ogre	Latvia	LV-5001
18	Clinical Research Centre "Riga" - Katrinas dambis 16	Riga	Latvia	LV-1045
19	Talsu Hospital - Rugena street 7	Talsi	Latvia	LV-3201
20	NZOZ Specjalistyczny Ośrodek, Internistyczno-Diabetologiczny, ul Zamenhofa 10/20	Białystok	Poland	15-435
21	Centrum Neurologii Klinicznej - Ul. Dwernickiego 8	Kraków	Poland	31-530
22	NZOZ Special-Med. Ul. Weteranów 46	Lublin	Poland	20-044
23	NZOZ MEDICA, ul. Jutrzenki 4	Lublin	Poland	20-538
24	NZOZ Beta-Med., Plac Wolności 17	Rzeszów	Poland	35-073
25	Adamiec Rajmund Gabinet Lekarski, ul. Żelazna 34	Wrocław	Poland	53-428
26	Centre of Neurology, Clinical Hospital Centre "Dr Dragisa Misovic"	Belgrade	Serbia	11000
27	Clinic for Neurology and Psychiatry, Clinical Hospital Centre "Zvezdara"	Belgrade	Serbia	11000
28	Institute for Endocrinology, Clinical Centre Serbia	Belgrade	Serbia	11000
29	Neurology Clinic, Military Medical Academy	Belgrade	Serbia	11000
30	Neurology Department, Clinical Hospital Zemun	Belgrade	Serbia	11000
31	Center for Neurology, Clinical Centre "Kragujevac"	Kragujevac	Serbia	34000

Sponsors and Collaborators

Hoffmann-La Roche
Ergomed GmbH

Investigators

Study Chair: Jean-Louis Abitbol, MD, Trophos, Parc Scientifique de Luminy - Case 931, Luminy Biotech Enterprises, 13288 Marseille Cedex9 - France
Principal Investigator: Dan Ziegler, MD, German Diabetes Center, German Diabetes Clinic, Leibniz Institute at the Heinrich-Heine University, Auf ´m Hennekamp 65, 40225 Dusseldorf, Germany