Use of Duloxetine or Pregabalin in Monotherapy versus Combination Therapy of Both Drugs in Patients with Painful Diabetic Neuropathy The COMBO (COmbination vs Monotherapy of pregaBalin and dulOxetine) Study - HMGQ

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2009-010063-16-IT
• Date of registration: 12/03/2010
• Prospective Registration: No
• Primary sponsor: ELI LILLY
• Public title: Use of Duloxetine or Pregabalin in Monotherapy versus Combination Therapy of Both Drugs in Patients with Painful Diabetic Neuropathy The COMBO (COmbination vs Monotherapy of pregaBalin and dulOxetine) Study - HMGQ
• Scientific title: Use of Duloxetine or Pregabalin in Monotherapy versus Combination Therapy of Both Drugs in Patients with Painful Diabetic Neuropathy The COMBO (COmbination vs Monotherapy of pregaBalin and dulOxetine) Study - HMGQ
• Date of first enrolment: 16/02/2010
• Target sample size: 1120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010063-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 4

Countries of recruitment

France, Germany, Greece, Italy, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male or female outpatients (at least 18 years of age).[2] Pain due to bilateral peripheral neuropathy.[3] Score of at least 4 on the 24-hour average pain severity score on an 11-point Likert scale (on BPI Modified Short Form).[4]Patient is currently not receiving treatment for DPNP or was receiving treatment for DPNP, with a drug other than pregabalin or duloxetine, and completed the required washout prior to randomization.[5] Patient has never received treatment with duloxetine or pregabalin.[6] Stable glycaemic control, as assessed by a physician investigator, and (HbA1c)equal or less than 12% at inclusion.[7]Patient has a level of understanding sufficient to provide written informed consent and to communicate with the investigator and site personnel.[8] Patient is judged to be reliable, agrees to keep all appointments for clinic visits, and agrees to participate in recording responses to questionnaires and other instruments used in this study, as well as all other protocol procedures.[9] All females of child-bearing potential must test negative for pregnancy at Visit 1, based on a serum pregnancy test. Females of child-bearing potential must agree to use a medically acceptable and reliable means of birth control during the study and for 1 month following the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[10]Have a known hypersensitivity to duloxetine or pregabalin or any of the inactive ingredients or have any contraindication for the use of duloxetine or pregabalin.[11]Have uncontrolled narrow-angle glaucoma.[12] Have previously completed or withdrawn from this study or any other study investigating duloxetine or pregabalin or have previously been treated with duloxetine or pregabalin.[13]Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of Visit 2, or have a potential need to use a MAOI during the study or within 5 days of discontinuation of study drug.[14]Have received fluoxetine within 30 days prior to Visit 2.[15]Have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C). [16]Have a serum creatinine greater than or equal 1.5 mg/dL or a creatinine clearance <60 mL/min, at Visit 1.[17]Are judged clinically by the investigator to be at suicidal risk or as defined by a score of 2 or greater on Question 9 of the BDI-II, at Visit 1 or Visit 2.[18]Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine.[19]Exclusion criterion [19] has been deleted.[20] Women who are breast-feeding.[21]Have a historical exposure to drugs known to cause neuropathy (for example, vincristine), or a history of a medical condition, including pernicious anaemia and hypothyroidism, that could have been responsible for neuropathy.[22]Have pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the DPNP.[23] Are investigator site personnel directly affiliated with this study and/or their immediate families.[24] Are employed by Lilly or Boehringer Ingelheim.[25]At the time of study entry (Visit 1), are currently enrolled in, or have been discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [26]Have serious or unstable cardiovascular, hepatic, renal, respiratory or haematological illness; symptomatic peripheral vascular disease; a history of seizure disorder; or other medical (including unstable hypertension and not clinically euthyroid) or psychological conditions that, in the opinion of the investigator, would compromise participation or be likely to require hospitalisation during the course of the study. [27]Have a history of frequent and/or severe allergic reactions with multiple medications. [28]Are currently taking any excluded medications that cannot be discontinued at Visit 1. [29]Have any exclusion criteria required by local law. [30]Have received non-pharmacological treatment for pain within 14 days prior to Visit 2, or do not agree to abstain from non-pharmacological treatment during the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

diabetic peripheral neuropathic pain (DPNP)
MedDRA version: 14.1 Level: LLT Classification code 10054095 Term: Neuropathic pain System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: CYMBALTA
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: Duloxetine
Concentration unit: mg milligram(s)
Concentration number: 30-

Trade Name: CYMBALTA
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: Duloxetine
Concentration unit: mg milligram(s)
Concentration number: 60-

Trade Name: LYRICA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PREGABALIN
Concentration unit: mg milligram(s)
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): The BPI Modified Short Forma is a self-reported instruments thet measures the severity of pain and the interface of pain on function. The primary efficacy measure will be the BPI Modified Short Form 24-hour average pain item score. This measures the severity of pain aver the previous 24 hours.

Secondary Objective: To evaluate the efficacy of a duloxetine and pregabalin standard doses combination therapy versus a maximal dose of monotherapy with either pregabalin or duloxetine: -on the following measures,over an 8-week period:Mean change in items of the BPI Modified Short Form Severity and Interference portions;Means on the CGI-I and PGI-I scales;Response rates defined;Mean change in pain components on the NPSI questionnaire. -on mood symptoms (HADS) -on functional/healt outcomes as mesaured by mean changes on the SDS. To evaluate the safety of a duloxetine and pregabalin standard doses combination therapy versus a maximal dose of monotherapy with either pregabalin or duloxetine as measured by discontinuation rates, treatment-emergent adverse events (TEAEs) and vital signs. To compare the effect of a maximal dose of duloxetine monotherapy versus a standard dose of duloxetine and pregabalin combination therapy oon resource utilisation.

Main Objective: To evaluate whether treatment at standard doses with duloxetine (60 mg/day) in combination with pregabalin (300 mg/day) is superior to a maximal dose of duloxetine (120 mg/day) or pregabalin (600 mg/day) given as monotherapy, over an 8-week period, in patients with diabetic peripheral neuropathic pain (DPNP), who don't respond to a standard dose of either duloxetine or pregabalin after 8 weeks of initial treatment.

Secondary ID(s)

F1J-EW-HMGQ

2009-010063-16-NL