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Painful Diabetic NeuropathyPhase 2NCT02068027

Study of Clonidine Hydrochloride Topical Gel, 0.1% in the Treatment of Pain Associated With Diabetic Neuropathy

A Phase 2 study testing Clonidine Gel 0.1% in people with Painful Diabetic Neuropathy and Diabetic Neuropathy, run by BioDelivery Sciences International at 23 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 the study is to determine whether clonidine gel is an effective treatment for reducing the pain associated with painful diabetic neuropathy. Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Clonidine Gel 0.1%
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
260 participants
Where
23 sitesUnited States
Study dates
Mar 2014to Mar 2015
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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The subject has provided written informed consent.
  • The subject is an outpatient aged 18 to 85 years (inclusive) at the time of the Screening Visit.
  • The subject has Type 1 or Type 2 diabetes mellitus with glycemic control that has been optimized and has been stable on diet therapy, oral anti-hyperglycemic agents and/or insulin, for at least three (3) months prior to the Screening Visit.
  • The subject must be a male or non-pregnant, non-lactating female. Females must be practicing an acceptable method of birth control, or be surgically sterile or postmenopausal (amenorrhea for ≥12 months). Non-pregnancy will be confirmed (as applicable) by a pregnancy test conducted at the Screening and Randomization Visits. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
  • The subject has chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for at least three (3) months. A loss of distal sensation and/or tingling paresthesia primarily in the toes and fingers is acceptable, but must be of secondary importance to the distal neuropathic pain. Pain should be clearly localized to the area of neuropathy (feet) and subjects should be able to distinguish this pain (the target pain) from other painful areas and conditions.
  • The subject has an average pain score relevant to the target pain in the feet of ≥4 on an 11-point Numeric Pain Rating Scale over the previous 24 hours at Screening.
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  • The subject has a pain score of at least 2, on the 11-point Numeric Pain Rating Scale , within 30 minutes following topical 0.1% capsaicin application with occlusive dressing to the pretibial area.
  • The subject has a mean daily average pain score relevant to the target pain in the feet of ≥4 on an 11-point Numeric Pain Rating Scale during the Baseline Phase.
  • The subject has met the pain evaluation and scoring criteria at the end of the Placebo Lead-in Phase by having a mean daily average pain score relevant to the target pain in the feet of ≥4 on an 11-point Numeric Pain Rating Scale without having a decrease in their pain score greater than 20% compared to the Baseline Phase score in the 11-point Numeric Pain Rating Scale .
  • The subject has been medically stable for at least 30 days prior to the Screening Visit, and in the opinion of the Investigator, is in otherwise good general health based on medical history, physical examination, ECG, and laboratory evaluation.
  • If taking chronic oral pain medications, the subject must be on a stable regimen for at least 14 days prior to the Baseline Visit with the expectation that the medications, dose(s) and schedule will remain stable throughout the study. For medications containing non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, subjects must be on a stable dose for at least 7 days prior to the Baseline Visit. As needed pain medications will be limited to acetaminophen from Day -8 until the end of the treatment period. Low dose aspirin (81 mg/day) is not considered as analgesic therapy.
  • Subject is compliant with daily pain assessments during the Baseline Phase and Placebo Lead in Phase of the study by recording their Numeric Pain Rating Scale score at least 5 days and the last 3 days of the previous 7 days.
  • Subject is alert and has the capabilities of applying topical gel to both feet three times daily. A caregiver, trained by the study staff to apply study drug, would be a suitable alternative to self-application of the treatment.

Who cannot join

  • The subject has neuropathy secondary to non-diabetic causes in the opinion of the Investigator (e.g., significant vasculitis, collagen vascular disorder, familial neuropathy, alcoholism, pernicious anemia, hepatitis, malignancy, syphilis, post-herpetic neuralgia, chronic inflammatory demyelinating polyradiculopathy, human immunodeficiency virus [HIV], medication-induced neuropathy, vitamin B12 deficiency).
  • The subject has a significant neurological disorder or a condition that can cause symptoms that mimic peripheral neuropathy or might confound assessment of painful diabetic neuropathy (e.g., stroke with distal neurological deficit, mononeuritis multiplex, lumbar radiculopathy, multiple sclerosis) or has significant asymmetric neuropathic signs and symptoms.
  • The subject has other sustained pain with intensity at or greater than the bilateral neuropathic pain in the feet/toes.
  • The subject is using an implanted medical device (e.g., spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for the treatment of pain.
  • The subject has no pin-prick sensitivity to Neuropen testing of non-calloused areas of the foot.
  • The subject is clinically hypotensive with a resting diastolic blood pressure <60 mm Hg or a systolic blood pressure <90 mm Hg.
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  • The subject has recent history (within the past 3 months) or current symptoms of orthostatic hypotension with a sudden fall in blood pressure on standing accompanied by dizziness and lightheadedness.
  • The subject has a history of foot or toe amputation, or an active foot or toe ulcer.
  • The subject has any significant or unstable medical or psychiatric condition that, in the opinion of the Investigator, would interfere with his/her ability to participate in the study.
  • The subject has a history of substance abuse disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) within the past year, has current evidence for substance abuse disorder, is receiving medicinal treatment for drug abuse, or tests positive upon urine drug screen for a non-prescribed substance of abuse.
  • The subject has used capsaicin on the feet for greater than 2 consecutive weeks in the previous 3 months.
  • The subject has symptomatic or severe coronary insufficiency, clinically significant cardiac conduction disturbances, myocardial infarction (within last 12 months), moderate to severe cerebrovascular disease, or severe chronic obstructive pulmonary disease (COPD) requiring oxygen therapy.
  • The subject has a serum creatinine value >2.0 mg/dL or a value for alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 times the upper limit of normal at Screening.
  • The subject was dosed with an investigational drug within 30 days prior to the Screening Visit.
  • The subject is likely to be noncompliant or unreliable in providing pain ratings as judged by the Investigator.
  • The subject has evidence of clinically significant peripheral vascular disease as evidenced by history of intermittent claudication or evidence of vascular ulcers, including venous stasis ulcers.
  • The subject has had prior treatment with clonidine topical gel.
  • The subject is currently taking or has taken clonidine in any form (oral, transdermal patch) over the past 4 weeks.
  • The subject has known hypersensitivity or intolerance to clonidine.
  • Except for acetaminophen, the subject is currently receiving any medications that could affect neuropathic pain and is not at a stable dose for at least 14 days prior to the Baseline Visit (other than medications containing NSAIDs and aspirin which must be stable for 7 days prior to the Baseline Visit).
  • The subject is receiving non-oral pain medication(s) (transdermal, topical, subcutaneous, intramuscular, intravenous, intrarectal, sublingual, transmucosal) and/or using "alternative medicine" products or techniques (acupuncture, naturopathy, homeopathy, etc.) for pain treatment ≤7 days prior to the Baseline Visit.
  • Subject has a history of malignancy within the past 5 years with the exception of successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix.
  • The subject has been hospitalized within 30 days of the Screening Visit, or is planning to have surgery during the study period.
  • The subject has clinical evidence of pedal edema or venous stasis disease associated with significant skin changes on physical examination.
  • The subject has a clinically relevant painful foot condition, such as tarsal tunnel syndrome, plantar fasciitis, Morton's neuroma, painful bunion, or arthritis of the foot/ankle, or has a condition that may be associated with numbness in the foot.
  • The subject has any dermatologic condition of the lower extremities that could affect study drug absorption (e.g., severe edema).
  • The subject has current symptoms of depression with a Beck Depression Inventory -II score >19 at Screening.

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • Study site

    Bradenton, Florida, 34205

  • Study site

    Brandon, Florida, 33511

  • Study site

    Columbus, Georgia, 31904

  • Study site

    Dallas, Texas, 75230

  • Study site

    Evansville, Indiana, 47714

  • Study site

    Hazelwood, Missouri, 63042

  • Study site

    Houston, Texas, 77055

  • Study site

    Jupiter, Florida, 33458

  • Study site

    Kansas City, Kansas, 66160

  • Study site

    Miami, Florida, 33143

  • Study site

    Milford, Connecticut, 06460

  • Study site

    Mt. Pleasant, South Carolina, 29464

  • Study site

    Phoenix, Arizona, 85023

  • Study site

    Renton, Washington, 98057

  • Study site

    San Antonio, Texas, 78229

  • Study site

    Santa Monica, California, 90404

  • Study site

    Tampa, Florida, 33606

  • Study site

    Virginia Beach, Virginia, 23451

  • Study site

    Walnut Creek, California, 94598

  • Study site

    Warwick, Rhode Island, 02886

  • Study site

    Waterbury, Connecticut, 06708

  • Study site

    West Palm Beach, Florida, 33401

  • Study site

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: A Multicenter Randomized, Double-Blind, Placebo-Controlled, 2-Arm Parallel-Group Study to Determine the Efficacy and Safety of Clonidine Hydrochloride Topical Gel, 0.1% in the Treatment of Pain Associated With Painful Diabetic Neuropathy

The purpose of the study is to determine whether clonidine gel is an effective treatment for reducing the pain associated with painful diabetic neuropathy.

Read the detailed description

Study CLO 290 was a multicenter, randomized, double blind, placebo controlled, 2 arm parallel group study of Clonidine Gel in the treatment of pain associated with PDN. Subjects were randomly assigned in a 1:1 ratio to receive 1 of 2 treatments applied topically TID to both feet for 85 days: Clonidine Gel (3.9 mg of clonidine HCl total daily dose), or Placebo Gel (vehicle without clonidine). Approximately 140 adult subjects with symmetrical distal PDN were expected to be randomized into the study. However, a pre-planned fully blinded interim analysis was performed when 70 subjects had completed the study for the purpose of re estimating sample size. Following the recommendation of the independent, third party statistician who conducted the interim analysis, the sample size was adjusted to allow approximately 260 subjects to be randomized into the study.

The study included 5 phases: Screening Phase (up to 21 days duration), Baseline Phase (Day 14 to Day 8), Placebo Lead in Phase (Day -7 to Day 1), Double blind Treatment Phase (85 days), and a Post-treatment Follow up Phase (7 days, only for subjects not enrolling in the open label long term safety study, CLO 311).

Being tested
Clonidine Gel 0.1%, Placebo
Keywords
Diabetes Mellitus, Pain, Foot pain, Neuropathy
Medical subject headings
Diabetic Neuropathies, Diabetes Mellitus, Pain

What participants receive

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

  • Clonidine Gel 0.1%Drug

  • PlaceboDrug

Study groups in NCT02068027
Study groupRoleWhat they receive
Clonidine Gel 0.1%ExperimentalClonidine hydrochloride topical gel, 0.1%
Receives: Drug: Clonidine Gel 0.1%
PlaceboPlacebo comparatorPlacebo gel of identical appearance as active treatment
Receives: Drug: Placebo

What is being measured

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

  1. Change From Baseline to Day 84 (Week 12) in Numeric Pain Rating Scale Score

    The Numeric Pain Rating Scale is a single reading that measures the patients interpretation of their pain on a scale from 0, no pain to 10, worst pain imaginable. The change from baseline can range from -10 to 10. The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "average pain in the past 24 hours in the painful areas of the feet" averaged over Days 78 to 84 compared to the 7 days at the Baseline Phase (Days -14 to -8). For the primary efficacy endpoint, the mean change in pain intensity from Baseline to Week 12 was analyzed using an analysis of covariance (ANCOVA) model with the Baseline pain intensity score serving as a covariate. The statistical model also included treatment, site, site by treatment interaction, and strata. If the site by treatment interaction term was not significant at the 0.1 level, then it was excluded from the model.

    Measured: The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days])

Secondary outcomes (1)

  1. Mean Daily Worst Pain Intensity Numeric Pain Rating Scale Scores

    The Numeric Pain Rating Scale is a single reading that measures the patients interpretation of their pain on a scale from 0, no pain to 10, worst pain imaginable. The change from baseline can range from -10 to 10. The change from Baseline (worst score from Day -14 to Day -8) to End-of-Treatment (worst score during Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "worst pain in the past 24 hours in the painful areas of the feet" from Days 78 to 84 compared to the 7 days at the Baseline Phase (Days -14 to -8). For the endpoint, the change in worst pain intensity from Baseline to Week 12 was analyzed using an analysis of covariance (ANCOVA) model with the Baseline worst pain intensity score serving as a covariate. The statistical model also included treatment, site, site by treatment interaction, and strata. If the site by treatment interaction term was not significant at the 0.1 level, then it was excluded from the model.

    Measured: The change from Baseline (worse over Day -14 to Day -8) to End-of-Treatment (worse over Days 78 to 84 [±3 days])

Timeline

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

  1. First posted20 Feb 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionMar 2015
  4. Study completionMar 2015

Resources

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
260 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02068027
Sponsor's protocol ID
CLO-290
Status last verified
Aug 2017
First submitted
19 Feb 2014
Last updated
26 Sep 2017
Data monitoring committee
No
Individual data sharing
No

Publications

  • Serednicki WT, Wrzosek A, Woron J, Garlicki J, Dobrogowski J, Jakowicka-Wordliczek J, Wordliczek J, Zajaczkowska R. Topical clonidine for neuropathic pain in adults. Cochrane Database Syst Rev. 2022 May 19;5(5):CD010967. doi: 10.1002/14651858.CD010967.pub3.

    PubMed 35587172

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clonidine Gel 0.1% in people with Painful Diabetic Neuropathy and Diabetic Neuropathy, run by BioDelivery Sciences International at 23 sites in United States.

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 13 inclusion and 27 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 26 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 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 24 Aug 2017). 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 to Day 84 (Week 12) in Numeric Pain Rating Scale Score (time frame: The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days])). 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 NCT02068027, which also lists 1 linked publication.

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 26 Sep 2017.

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