Peripheral NeuropathyPhase 2NCT00603265

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

A Phase 2 study testing ADL5859 and Duloxetine in people with Peripheral Neuropathy and Neuropathic Pain, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 27 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Peripheral Neuropathy, Neuropathic Pain
What is being tested?: ADL5859 and Duloxetine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 226 participants
Where: 27 sitesUnited States
Study dates: Nov 2007to Aug 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 12Show fewer

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

Who cannot join

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

Show all 13Show fewer

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

Trial locations and contacts

27 sites in 1 country.

City, postcode or hospital

27 sites in 1 country

United States27 sites

Advanced Regional Center for Clinical Research (Ankle & Foot Care)
Altoona, Pennsylvania, 16602
Clnical Study Center of Asheville
Asheville, North Carolina, 28801
Beacon Clinical Research
Brockton, Massachusetts, 02301
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Healthcare Research
Florissant, Missouri, 63031
Nerve & Muscle Center of Texas
Houston, Texas, 77030
FPA Clinical Research
Kissimmee, Florida, 34741
Innovative Research of West Florida, Inc.
Largo, Florida, 33770
Advanced Biomedical Research of America
Las Vegas, Nevada, 89123
The Pain Treatment Center of the Bluegrass
Lexington, Kentucky, 40503
Panhandle Family Care Associates & Emerald Coast Research Grp, Inc.
Marianna, Florida, 32446
Clinical Research Consultants, Research Department
Medford, Oregon, 97504
Radiant Research-Akron
Mogadore, Ohio, 44260
Renstar Medical Research
Ocala, Florida, 34471
Creighton Diabetes Center, Creighton Univ. Sch. of Medicine
Omaha, Nebraska, 68131
Radiant Research-St.Petersburg
Pinellas Park, Florida, 33781
Integrated Research Group
Riverside, California, 92506
Invisions Consultants LLC
San Antonio, Texas, 78217
Diabetes & Glandular Disease Research Associates
San Antonio, Texas, 78229
S.A.M. Clinical Research Center
San Antonio, Texas, 78229
Doctor's Research Network
South Miami, Florida, 33143
Neurology & Neuroscience Center of Ohio
Toledo, Ohio, 43623
Torrance Clinical Research
Torrance, California, 90505
Tidewater Integrated Medical Research
Virginia Beach, Virginia, 23451
Metabolic Research Institute, Inc.
West Palm Beach, Florida, 33401
Laszlo J. Mate, MD
West Palm Beach, Florida, 33407
Aquilo Research
Yukon, Oklahoma, 73099

Other trials in United States

About this study

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

Read the 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.

Conditions: Peripheral Neuropathy, Neuropathic Pain
Being tested: ADL5859, Duloxetine, Placebo
Keywords: Diabetic Peripheral Neuropathy, Neuropathic Pain
Medical subject headings: Peripheral Nervous System Diseases, Neuralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ADL5859Drug
DuloxetineDrug
Also called Cymbalta
PlaceboDrug

Study groups in NCT00603265
Study group	Role	What they receive
ADL5859	Experimental	2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days Receives: Drug: ADL5859
Duloxetine	Active comparator	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 Receives: Drug: Duloxetine; Drug: Placebo
Placebo	Placebo comparator	2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, Week 4

Secondary outcomes (6)

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.
Measured: Baseline, Week 4
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.
Measured: Week 4
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.
Measured: Baseline, 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.
Measured: Baseline, 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.
Measured: Baseline, Week 1, Week 2, Week 3, Week 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.
Measured: Baseline, Week 1, Week 2, Week 3, Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2007Aug 2008

First posted29 Jan 2008 (estimated)
Study startNov 2007
Primary completionAug 2008
Study completionAug 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Peripheral NeuropathyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 226 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00603265
Sponsor's protocol ID: 33CL231
Status last verified: Jun 2015
First submitted: 17 Jan 2008
Last updated: 1 Jul 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruitingObservational study
Postural Control and Balance Performance in Patients With Carpal Tunnel Syndrome
Carpal Tunnel Syndrome (CTS), Postural Assessment
Active, not recruiting
The AIUR Trial: Surgical Gloves to Prevent Peripheral Neuropathy
Chemotherapy-induced Peripheral Neuropathy
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis

All Peripheral Neuropathy trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00603265
Acronym / sponsor ID: 33CL231
Conditions: Peripheral Neuropathy, Neuropathic Pain
Keywords: Diabetic Peripheral Neuropathy, Neuropathic Pain
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 226 participants (actual)
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: Nov 2007
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 29 Jan 2008 (estimated)
Results: Posted 1 Jul 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
ADL5859	Experimental	Drug: ADL58592 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
Duloxetine	Active comparator	Drug: Duloxetine, Drug: Placebo2 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
Placebo	Placebo comparator	Drug: Placebo2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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)

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ADL5859	Drug	ADL5859
DuloxetineAlso: Cymbalta	Drug	Duloxetine
Placebo	Drug	Duloxetine, Placebo

Primary outcome

Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score
Time frame: Baseline, 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 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.

6 secondary outcomes

Percentage of Responders
Time frame: Baseline, Week 4
Patient Global Impression of Change (PGIC)
Time frame: Week 4
Change in Sleep Interference Scale (SIS) From Baseline
Time frame: Baseline, Week 4
Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score
Time frame: Baseline, Week 4
Change From Baseline in NPRS at Rest in the Clinic
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4
Change From Baseline in NPRS After Walking 50 Feet in the Clinic
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4

Results and safety

Results posted to the registry on 1 Jul 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ADL5859	76	69
Duloxetine	78	62
Placebo	72	67

Primary outcome: Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score

Time frame: Baseline, Week 4. Least squares mean (Standard Error). Unit: units on a scale

Measure	ADL5859 n = 75	Duloxetine n = 77	Placebo n = 72
Value	1.02 (0.225)	1.74 (0.221)	1.51 (0.229)

Population analysed: All participants who received at least 1 dose of study medication and had evaluable NPRS data. Baseline-observation-carried-forward (BOCF) was used to impute missing postbaseline values for participants who were discontinued from the study early.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ADL5859	0 of 75 (0%)	27 of 75 (36%)	Not reported
Duloxetine	1 of 78 (1.3%)	28 of 78 (35.9%)	Not reported
Placebo	0 of 72 (0%)	27 of 72 (37.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Peripheral Neuropathy

Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruitingObservational study
Postural Control and Balance Performance in Patients With Carpal Tunnel Syndrome
Carpal Tunnel Syndrome (CTS), Postural Assessment
Active, not recruiting
The AIUR Trial: Surgical Gloves to Prevent Peripheral Neuropathy
Chemotherapy-induced Peripheral Neuropathy
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bruce Berger, MD study director

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

27 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score (time frame: Baseline, Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00603265.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2015.