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Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

Primary Purpose

Peripheral Neuropathy, Neuropathic Pain

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ADL5859
Duloxetine
Placebo
Sponsored by
Cubist Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Neuropathy focused on measuring Diabetic Peripheral Neuropathy, Neuropathic Pain

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female participants between 18 and 75 years of age, inclusive
  • Body weight of at least 45 kilograms (kg)
  • Diabetes mellitus (type I or II) that is documented to be under stable glycemic control over a period of at least 3 months, as indicated by a glycosylated hemoglobin (HbgAIC) of less than or equal to 12% and a stable dose of insulin or oral diabetic medication for 90 days prior to starting study medication
  • No change in diabetic medications is planned for the duration of the study
  • Evidence of symmetrical, bilateral pain in the lower extremities due to diabetic peripheral neuropathy (DPN)
  • Presence of daily pain due to DPN for at least 3 months
  • Score greater than or equal to 3 on the physical examination portion of the Michigan Neuropathy Screening Instrument (MNSI)
  • Average weekly pain score of greater than or equal to 4 on the numeric pain rating scale (NPRS) for symmetrical neuropathic pain in the feet and legs
  • For male participants, be surgically sterile or agree to use an appropriate method of contraception
  • For female participants of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the Food and Drug Administration (FDA)
  • Be willing and able to comply with the protocol requirements
  • Be able to understand and willing to provide written informed consent in English

Exclusion Criteria:

  • Presence of pain conditions that cannot be distinguished from DPN
  • Presence of significant renal disease, as indicated by a serum creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL), or presence of significant hepatic disease
  • Have a history of a seizure disorder
  • Presence of serious or unstable cardiovascular disease, respiratory disease, hematologic illness, or a psychiatric condition
  • History of evidence of symptomatic orthostatic hypotension
  • History of a major depressive disorder, generalized anxiety disorder, eating disorder, or substance abuse (including alcohol) within the past year
  • History or evidence of mania, bipolar disorder, or psychosis
  • History of allergy to acetaminophen or duloxetine
  • Score of greater than or equal to 18 on the Beck Depression Inventory II (BDI-II) or score of greater than zero on Item 9 of the BDI-II
  • Use of any of the following concomitant medications: fluvoxamine; quinolone antimicrobials (ciprofloxacin and enoxacin); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants; opioids; nonsteroidal anti-inflammatory drugs (NSAIDS); anticonvulsants; aspirin (with the exception of low-dose aspirin as cardiovascular prophylaxis); or cytochrome P4503A (CYP3A) and P-glycoprotein transporter inhibitors
  • Pregnant, lactating, or plans to become pregnant during the study
  • Presence of foot or toe amputation
  • Participation in another study with an investigational compound within the previous 30 days prior to study medication administration, or concurrent participation in another clinical study

Sites / Locations

  • Integrated Research Group
  • Torrance Clinical Research
  • FPA Clinical Research
  • Innovative Research of West Florida, Inc.
  • Panhandle Family Care Associates & Emerald Coast Research Grp, Inc.
  • Renstar Medical Research
  • Radiant Research-St.Petersburg
  • Doctor's Research Network
  • Metabolic Research Institute, Inc.
  • Laszlo J. Mate, MD
  • The Pain Treatment Center of the Bluegrass
  • Beacon Clinical Research
  • Healthcare Research
  • Creighton Diabetes Center, Creighton Univ. Sch. of Medicine
  • Advanced Biomedical Research of America
  • Clnical Study Center of Asheville
  • Radiant Research-Akron
  • Neurology & Neuroscience Center of Ohio
  • Aquilo Research
  • Clinical Research Consultants, Research Department
  • Advanced Regional Center for Clinical Research (Ankle & Foot Care)
  • Altoona Center for Clinical Research
  • Nerve & Muscle Center of Texas
  • Invisions Consultants LLC
  • Diabetes & Glandular Disease Research Associates
  • S.A.M. Clinical Research Center
  • Tidewater Integrated Medical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

ADL5859

Duloxetine

Placebo

Arm Description

2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days

2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days

2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Outcomes

Primary Outcome Measures

Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score
The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained up to 3 times per day over a 7-day period. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment group as a main factor and baseline NPRS score as a covariate. Change from Baseline = NPRS at baseline - NPRS at Week 4; a positive number in the LS mean indicates a reduction in pain intensity from baseline.

Secondary Outcome Measures

Percentage of Responders
A responder was defined as a participant who showed a reduction in average pain (as measured by NPRS) of at least 30% from baseline to Week 4. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The percentage of participants who qualified as responders is presented per treatment arm.
Patient Global Impression of Change (PGIC)
PGIC is a participant-rated instrument that measures the change in the participant's overall status for the previous 2 weeks based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The number of participants in each category is presented.
Change in Sleep Interference Scale (SIS) From Baseline
Sleep Interference was assessed on an 11-point Numeric Rating Scale where a score of 0 indicated "pain did not interfere with sleep" and a score of 10 indicated "pain completely interfered with sleep". Here, "n" signifies "Number of participants" for Baseline and Month 3 telephone interview whereas "n" signifies "number of observations" for Month 1, 2, and 3 because a participant could have had multiple visits during Month 1, 2, and 3 as this was a non-interventional study with no scheduled study visits, except Baseline visit and the Month 3 telephone interview. LS means were calculated using ANCOVA with treatment group as a main factor and baseline SIS score as a covariate. Change from baseline = SIS score at baseline - SIS score at Week 4.
Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score
At each of the evening pain assessments, participants assessed their overall pain intensity over the preceding 24 hours using NPRS. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained at Baseline and Week 4. Change from baseline = NPRS at baseline - NPRS at Week 4.
Change From Baseline in NPRS at Rest in the Clinic
The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken while the participant was at rest. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.
Change From Baseline in NPRS After Walking 50 Feet in the Clinic
The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken after the participant walked 50 feet in the clinic. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.

Full Information

First Posted
January 17, 2008
Last Updated
June 4, 2015
Sponsor
Cubist Pharmaceuticals LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00603265
Brief Title
Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Official Title
A Phase 2a, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group, Multicenter Study to Assess the Safety and Efficacy of ADL5859 100 mg BID in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cubist Pharmaceuticals LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the effectiveness of ADL5859 in relieving the pain associated with diabetic peripheral neuropathy (DPN) compared with placebo and duloxetine (a marketed drug approved for the treatment of painful DPN). The pain symptoms of DPN are thought to be due to damage to nerves caused by the diabetes.
Detailed Description
Participants were permitted to take acetaminophen 650 to 975 mg every 4 to 6 hours (up to a total of 4 grams in 24 hours) as needed for pain relief.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Neuropathy, Neuropathic Pain
Keywords
Diabetic Peripheral Neuropathy, Neuropathic Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
226 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ADL5859
Arm Type
Experimental
Arm Description
2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
Arm Title
Duloxetine
Arm Type
Active Comparator
Arm Description
2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days
Intervention Type
Drug
Intervention Name(s)
ADL5859
Intervention Type
Drug
Intervention Name(s)
Duloxetine
Other Intervention Name(s)
Cymbalta
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score
Description
The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained up to 3 times per day over a 7-day period. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment group as a main factor and baseline NPRS score as a covariate. Change from Baseline = NPRS at baseline - NPRS at Week 4; a positive number in the LS mean indicates a reduction in pain intensity from baseline.
Time Frame
Baseline, Week 4
Secondary Outcome Measure Information:
Title
Percentage of Responders
Description
A responder was defined as a participant who showed a reduction in average pain (as measured by NPRS) of at least 30% from baseline to Week 4. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The percentage of participants who qualified as responders is presented per treatment arm.
Time Frame
Baseline, Week 4
Title
Patient Global Impression of Change (PGIC)
Description
PGIC is a participant-rated instrument that measures the change in the participant's overall status for the previous 2 weeks based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The number of participants in each category is presented.
Time Frame
Week 4
Title
Change in Sleep Interference Scale (SIS) From Baseline
Description
Sleep Interference was assessed on an 11-point Numeric Rating Scale where a score of 0 indicated "pain did not interfere with sleep" and a score of 10 indicated "pain completely interfered with sleep". Here, "n" signifies "Number of participants" for Baseline and Month 3 telephone interview whereas "n" signifies "number of observations" for Month 1, 2, and 3 because a participant could have had multiple visits during Month 1, 2, and 3 as this was a non-interventional study with no scheduled study visits, except Baseline visit and the Month 3 telephone interview. LS means were calculated using ANCOVA with treatment group as a main factor and baseline SIS score as a covariate. Change from baseline = SIS score at baseline - SIS score at Week 4.
Time Frame
Baseline, Week 4
Title
Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score
Description
At each of the evening pain assessments, participants assessed their overall pain intensity over the preceding 24 hours using NPRS. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained at Baseline and Week 4. Change from baseline = NPRS at baseline - NPRS at Week 4.
Time Frame
Baseline, Week 4
Title
Change From Baseline in NPRS at Rest in the Clinic
Description
The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken while the participant was at rest. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 4
Title
Change From Baseline in NPRS After Walking 50 Feet in the Clinic
Description
The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken after the participant walked 50 feet in the clinic. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female participants between 18 and 75 years of age, inclusive Body weight of at least 45 kilograms (kg) Diabetes mellitus (type I or II) that is documented to be under stable glycemic control over a period of at least 3 months, as indicated by a glycosylated hemoglobin (HbgAIC) of less than or equal to 12% and a stable dose of insulin or oral diabetic medication for 90 days prior to starting study medication No change in diabetic medications is planned for the duration of the study Evidence of symmetrical, bilateral pain in the lower extremities due to diabetic peripheral neuropathy (DPN) Presence of daily pain due to DPN for at least 3 months Score greater than or equal to 3 on the physical examination portion of the Michigan Neuropathy Screening Instrument (MNSI) Average weekly pain score of greater than or equal to 4 on the numeric pain rating scale (NPRS) for symmetrical neuropathic pain in the feet and legs For male participants, be surgically sterile or agree to use an appropriate method of contraception For female participants of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the Food and Drug Administration (FDA) Be willing and able to comply with the protocol requirements Be able to understand and willing to provide written informed consent in English Exclusion Criteria: Presence of pain conditions that cannot be distinguished from DPN Presence of significant renal disease, as indicated by a serum creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL), or presence of significant hepatic disease Have a history of a seizure disorder Presence of serious or unstable cardiovascular disease, respiratory disease, hematologic illness, or a psychiatric condition History of evidence of symptomatic orthostatic hypotension History of a major depressive disorder, generalized anxiety disorder, eating disorder, or substance abuse (including alcohol) within the past year History or evidence of mania, bipolar disorder, or psychosis History of allergy to acetaminophen or duloxetine Score of greater than or equal to 18 on the Beck Depression Inventory II (BDI-II) or score of greater than zero on Item 9 of the BDI-II Use of any of the following concomitant medications: fluvoxamine; quinolone antimicrobials (ciprofloxacin and enoxacin); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants; opioids; nonsteroidal anti-inflammatory drugs (NSAIDS); anticonvulsants; aspirin (with the exception of low-dose aspirin as cardiovascular prophylaxis); or cytochrome P4503A (CYP3A) and P-glycoprotein transporter inhibitors Pregnant, lactating, or plans to become pregnant during the study Presence of foot or toe amputation Participation in another study with an investigational compound within the previous 30 days prior to study medication administration, or concurrent participation in another clinical study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce Berger, MD
Organizational Affiliation
Cubist Pharmaceuticals LLC
Official's Role
Study Director
Facility Information:
Facility Name
Integrated Research Group
City
Riverside
State/Province
California
ZIP/Postal Code
92506
Country
United States
Facility Name
Torrance Clinical Research
City
Torrance
State/Province
California
ZIP/Postal Code
90505
Country
United States
Facility Name
FPA Clinical Research
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
Facility Name
Innovative Research of West Florida, Inc.
City
Largo
State/Province
Florida
ZIP/Postal Code
33770
Country
United States
Facility Name
Panhandle Family Care Associates & Emerald Coast Research Grp, Inc.
City
Marianna
State/Province
Florida
ZIP/Postal Code
32446
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Radiant Research-St.Petersburg
City
Pinellas Park
State/Province
Florida
ZIP/Postal Code
33781
Country
United States
Facility Name
Doctor's Research Network
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Metabolic Research Institute, Inc.
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Laszlo J. Mate, MD
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
The Pain Treatment Center of the Bluegrass
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Beacon Clinical Research
City
Brockton
State/Province
Massachusetts
ZIP/Postal Code
02301
Country
United States
Facility Name
Healthcare Research
City
Florissant
State/Province
Missouri
ZIP/Postal Code
63031
Country
United States
Facility Name
Creighton Diabetes Center, Creighton Univ. Sch. of Medicine
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Advanced Biomedical Research of America
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89123
Country
United States
Facility Name
Clnical Study Center of Asheville
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Radiant Research-Akron
City
Mogadore
State/Province
Ohio
ZIP/Postal Code
44260
Country
United States
Facility Name
Neurology & Neuroscience Center of Ohio
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
Facility Name
Aquilo Research
City
Yukon
State/Province
Oklahoma
ZIP/Postal Code
73099
Country
United States
Facility Name
Clinical Research Consultants, Research Department
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
Advanced Regional Center for Clinical Research (Ankle & Foot Care)
City
Altoona
State/Province
Pennsylvania
ZIP/Postal Code
16602
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Nerve & Muscle Center of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Invisions Consultants LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Diabetes & Glandular Disease Research Associates
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
S.A.M. Clinical Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Tidewater Integrated Medical Research
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23451
Country
United States

12. IPD Sharing Statement

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Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

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