NCT01089556|CompletedPhase 3Results

A Study in Painful Diabetic Neuropathy

COMBO-DN

Use of Duloxetine or Pregabalin in Monotherapy Versus Combination Therapy of Both Drugs in Patients With Painful Diabetic Neuropathy "The COMBO - DN (COmbination vs Monotherapy of pregaBalin and dulOxetine in Diabetic Neuropathy) Study"

Eli Lilly and Company ClinicalTrials.gov

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2 other identifiers

13084F1J-EW-HMGQ

Study Type

interventional

Target

811

Locations

16 countries

Sites

Timeline

RegisteredMar 2010

StartedMar 2010

CompletionNov 2011

Brief Summary

This study will investigate the efficacy of a combination treatment of duloxetine + pregabalin compared with the maximal dose of each drug in monotherapy, in patients with diabetic peripheral neuropathic pain (DPNP) who have not responded to the standard recommended dose of either drug. It will provide an answer to a common clinical question, namely, is it better to increase the dose of the current monotherapy or to combine both treatments early on, in patients who do not respond to standard doses of duloxetine or pregabalin.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

811

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Mar 2010

Geographic Reach

16 countries

54 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.7 years study duration

Study Start

First participant enrolled

March 1, 2010

Completed

14 days until next milestone

First Submitted

Initial submission to the registry

March 15, 2010

Completed

3 days until next milestone

First Posted

Study publicly available on registry

March 18, 2010

Completed

1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2011

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2011

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

December 4, 2012

Completed

Last Updated

January 24, 2013

Status Verified

January 1, 2013

Enrollment Period

1.7 years

First QC Date

March 15, 2010

Results QC Date

October 30, 2012

Last Update Submit

January 17, 2013

Conditions

Diabetic Neuropathy, Painful

Outcome Measures

Primary Outcomes (1)

Change From Week 8 to Week 16 Endpoint in 24 Hour Average Pain Item Score on the Brief Pain Inventory (BPI) Modified Short Form
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Week 8, Week 16

Secondary Outcomes (14)

Mean Change From Week 8 to Week 16 Endpoint in Items of the Brief Pain Inventory (BPI) Modified Short Form Worst Pain Score
Week 8, Week 16
Percentage of Participants With a Reduction of Greater Than or Equal to 30% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint
Week 8 through Week 16
Percentage of Participants With a Reduction of Greater Than or Equal to 50% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint
Week 8 through Week 16
Percentage of Participants With a Decrease of Greater Than or Equal to 2 Points on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint
Week 8 through Week 16
Clinical Global Impression of Improvement (CGI-I) at Week 16 Endpoint
Week 16
+9 more secondary outcomes

Other Outcomes (16)

Mean Change From Baseline to Week 8 Endpoint in 24 Hour Average Pain Item Score on the Brief Pain Inventory (BPI) Modified Short Form
Baseline, Week 8
Percentage of Participants With a Reduction of Greater Than or Equal to 30% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 8 Endpoint
Baseline through Week 8
Percentage of Participants With a Reduction of Greater Than or Equal to 50% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 8 Endpoint
Baseline through Week 8
+13 more other outcomes

Study Arms (4)

Duloxetine

EXPERIMENTAL

Initial Treatment: Duloxetine 30 milligram (mg) daily for 1 week Duloxetine 60 mg daily for 7 weeks Intensive Treatment: Duloxetine 90 mg (60 mg in the morning, 30 mg in the evening) daily for 1 week Duloxetine 120 mg (60 mg twice daily) daily for 7 weeks

Drug: DuloxetineDrug: Placebo

Pregabalin+Duloxetine

EXPERIMENTAL

Initial Treatment: Pregabalin 150 mg daily for 1 week Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks Intensive Treatment: Pregabalin 300 mg (150 mg twice daily) daily for 8 weeks Duloxetine 30 mg daily for 1 week Duloxetine 60 mg daily for 7 weeks

Drug: DuloxetineDrug: PregabalinDrug: Placebo

Pregabalin

EXPERIMENTAL

Initial Treatment: Pregabalin 150 mg daily for 1 week Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks Intensive Treatment: Pregabalin 450 mg (300 mg in the morning, 150 mg in the evening) daily for 1 week Pregabalin 600 mg (300 mg twice daily) daily for 7 weeks

Drug: PregabalinDrug: Placebo

Duloxetine + Pregabalin

EXPERIMENTAL

Initial Treatment: Duloxetine 30 mg daily for 1 week Duloxetine 60 mg daily for 7 weeks Intensive Treatment: Duloxetine 60 mg daily for 8 weeks Pregabalin 150 mg daily for 1 week Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks

Drug: DuloxetineDrug: PregabalinDrug: Placebo

Interventions

DuloxetineDRUG

Administered orally

Also known as: Cymbalta, LY248686

DuloxetineDuloxetine + PregabalinPregabalin+Duloxetine

PregabalinDRUG

Administered orally

Duloxetine + PregabalinPregabalinPregabalin+Duloxetine

PlaceboDRUG

Administered orally, daily as a blind for duloxetine and/or pregabalin for 8 or 16 weeks

DuloxetineDuloxetine + PregabalinPregabalinPregabalin+Duloxetine

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Pain due to bilateral peripheral neuropathy (caused by type 1 or type 2 diabetes mellitus. Pain must begin in the feet, with relatively symmetrical onset. Daily pain should be present for more than 3 months \[assessed by questioning patient\]).
Score of at least 4 on the 24-hour average pain severity score on an 11-point Likert scale \[on Brief Pain Inventory (BPI) Modified Short Form\] at screening and at randomization.
Patient is currently not receiving treatment for diabetic peripheral neuropathic pain (DPNP) or was receiving treatment for DPNP, with a drug other than pregabalin or duloxetine, and completed the required washout
Patient has never received treatment with duloxetine or pregabalin. (However, a short course of less than 15 days of treatment, at any time previously, will be allowed.)
Stable glycemic control, as assessed by a physician investigator, and hemoglobin A1c (HbA1c) less than or equal to 12% at screening.

You may not qualify if:

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.
Have uncontrolled narrow-angle glaucoma.
Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to randomization, or have a potential need to use a MAOI during the study or within 5 days after discontinuation of study drug.
Have received fluoxetine within 30 days prior to randomization.
Have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
Have a serum creatinine greater than or equal to 1.5 milligram per deciliter (mg/dL) or a creatinine clearance less than 60 milliliter per minute (mL/min), at screening.
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 Beck Depression Inventory-II (BDI-II), at screening or randomization
Have a historical exposure to drugs known to cause neuropathy (for example, vincristine), or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy.
Have pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the DPNP.
Have serious or unstable cardiovascular, hepatic, renal, respiratory or hematological 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 hospitalization during the course of the study.
Have received non-pharmacological treatment for pain within 14 days prior to randomization, or do not agree to abstain from non-pharmacological treatment during the study.
Have a history of frequent and/or severe allergic reactions with multiple medications.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Eli Lilly and Companylead
Boehringer Ingelheimcollaborator

Study Sites (54)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Newcastle, New South Wales, 2292, Australia

Location

Warrawong, New South Wales, 2502, Australia

Location

Elizabeth Vale, South Australia, 5112, Australia

Location

Kelowna, British Columbia, V1Y 1Z9, Canada

Location

Vancouver, British Columbia, V6H 3X8, Canada

Location

Winnipeg, Manitoba, R3P 3P4, Canada

Location

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Cambridge, Ontario, N1R 7L6, Canada

Location

Laval, Quebec, H7T 2P5, Canada

Location

Osijek, 31000, Croatia

Location

Rijeka, HR-51000, Croatia

Location

Varaždin, 42000, Croatia

Location

Zagreb, 10000, Croatia

Location

Angers, 49933, France

Location

Bourges, 18000, France

Location

Juan-les-Pins, 06600, France

Location

Nevers, 58000, France

Location

Nîmes, 30029, France

Location

Paris, 75018, France

Location

Valenciennes, 59322, France

Location

Vierzon, 18100, France

Location

Vieux-Condé, 59690, France

Location

Dresden, 01307, Germany

Location

Schkeuditz, 04435, Germany

Location

Ampelokipoi, 11527, Greece

Location

Athens, 11521, Greece

Location

Melíssia, 15126, Greece

Location

Catania, 95100, Italy

Location

Milan, 20162, Italy

Location

Napoli, 80131, Italy

Location

Rome, 00161, Italy

Location

Mexico City, 38000, Mexico

Location

Eindhoven, 5623 EJ, Netherlands

Location

Maastricht, 6229 HX, Netherlands

Location

Bialystok, 15-445, Poland

Location

Lublin, 20-538, Poland

Location

Szczecin, 70-506, Poland

Location

Wroclaw, 50-127, Poland

Location

Seoul, 138-736, South Korea

Location

Girona, 17007, Spain

Location

Valencia, 46010, Spain

Location

Falköping, SE 52143, Sweden

Location

Huddinge, SE 141 86, Sweden

Location

Lund, 22185, Sweden

Location

Stockholm, 11522, Sweden

Location

Zurich, CH-8091, Switzerland

Location

Ankara, 06100, Turkey (Türkiye)

Location

Izmir, 35340, Turkey (Türkiye)

Location

Ashton-under-Lyne, Ashton-Under-Lyne, OL6 9RW, United Kingdom

Location

Chorley, Chorley, PR7 1PP, United Kingdom

Location

Manchester, Greater Manchester, M13 0JE, United Kingdom

Location

Ayrshire, Scotland, KA6 6DX, United Kingdom

Location

Nuneaton, Warwickshire, CV10 7BL, United Kingdom

Location

Livingston, West Lothian, EH54 6PP, United Kingdom

Location

MeSH Terms

Conditions

Diabetic Neuropathies

Interventions

Duloxetine HydrochloridePregabalin

Condition Hierarchy (Ancestors)

Peripheral Nervous System DiseasesNeuromuscular DiseasesNervous System DiseasesDiabetes ComplicationsDiabetes MellitusEndocrine System Diseases

Intervention Hierarchy (Ancestors)

ThiophenesSulfur CompoundsOrganic ChemicalsHeterocyclic Compounds, 1-RingHeterocyclic Compoundsgamma-Aminobutyric AcidAminobutyratesButyratesAcids, AcyclicCarboxylic AcidsAmino AcidsAmino Acids, Peptides, and Proteins

Results Point of Contact

Title: Chief Medical Officer
Organization: Eli Lilly and Company

Study Officials

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5AM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee: No
Restriction Type: GT60
Restrictive Agreement: Yes

Study Design

Study Type: interventional
Phase: phase 3
Allocation: RANDOMIZED
Masking: QUADRUPLE
Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose: TREATMENT
Intervention Model: PARALLEL
Sponsor Type: INDUSTRY
Responsible Party: SPONSOR

Study Record Dates

First Submitted

March 15, 2010

First Posted

March 18, 2010

Study Start

March 1, 2010

Primary Completion

November 1, 2011

Study Completion

November 1, 2011

Last Updated

January 24, 2013

Results First Posted

December 4, 2012

Record last verified: 2013-01

Locations

ES(2)DE(2)CA(6)CH(1)NL(2)ME(1)AU(3)CR(4)SE(4)GB(6)IT(4)PL(4)KR(1)TU(2)FR(9)GR(3)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Results Posted

Conditions

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (14)

Other Outcomes (16)

Study Arms (4)

Duloxetine

Pregabalin+Duloxetine

Pregabalin

Duloxetine + Pregabalin

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (54)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Study Design

Study Record Dates

Locations