Painful Diabetic NeuropathyPhase 2NCT02643251
The Efficacy and Safety of Clonidine Hydrochloride Topical Gel, vs Clonidine Hydrochloride Gel Comparator to Treat Painful Diabetic Neuropathy
A Phase 2 study testing Clonidine Hydrochloride Topical Gel, 0.1% and Clonidine Hydrochloride Gel Comparator in people with Painful Diabetic Neuropathy and Diabetic Neuropathy, run by BioDelivery Sciences International at 25 sites in United States.
Trial summary
The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who qualify to participate will apply study drug to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS) during the Treatment Phase for 12 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Painful Diabetic Neuropathy, Diabetic Neuropathy, Neuropathy
- What is being tested?
- Clonidine Hydrochloride Topical Gel, 0.1% and Clonidine Hydrochloride Gel Comparator
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 138 participants
- Where
- 25 sitesUnited States
- Study dates
- Dec 2015to Nov 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is fluent in English and has provided written informed consent.
- Subject is an outpatient ≥18 years of age at the time of the Screening Visit.
- Subject has Type 1 or Type 2 diabetes mellitus with a hemoglobin A1C value < 10% and has been stable on therapy (diet, oral anti-hyperglycemic, and/or insulin) for at least six (6) months prior to the Screening Visit.
- Subject is 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). A negative pregnancy test at the Screening and Day 1 visits is required for females of child-bearing potential. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
- Subject has chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for at least six (6) months. Pain should be clearly localized to the area of neuropathy (feet), and subjects should be able to distinguish the target pain from other painful areas and conditions.
- Subject has an average pain score relevant to the target pain in the feet of ≥4 on an 11 point numerical pain rating scale over the previous 24 hours at the Screening Visit.
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- Subject meets a pre-specified, minimum numerical pain rating scale score following capsaicin skin challenge.
- Subject must satisfactorily complete Accurate Pain Reporting and Minimizing Placebo Response Training.
- Subject must have moderate to severe pain during the Screening Run-in Phase.
- Subjects must be 75 to 110% compliant with application of study drug during the Screening Run-in Phase
- 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, electrocardiogram, and laboratory evaluation.
Who cannot join
- Subject has neuropathy secondary to non-diabetic causes in the opinion of the Investigator (e.g., vasculitis, familial neuropathy, alcoholism, pernicious anemia, hepatitis, malignancy, chronic inflammatory demyelinating polyneuropathy [CIDP], human immunodeficiency virus [HIV], medication-induced neuropathy, vitamin B12 deficiency).
- Subject has a significant neurological disorder or condition that might confound assessment of painful diabetic neuropathy (e.g., stroke with distal neurological deficit, mononeuritis multiplex, lumbar radiculopathy).
- Subject has a confounding disorder as determined by the Algorithm for Excluding Disorders that Masquerade as Painful Diabetic Neuropathy.
- Subject has other sustained pain with intensity at or greater than the bilateral neuropathic pain in the feet.
- Subject is using an implanted medical device (e.g., spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for treatment of pain.
- Subject is hypotensive with a resting diastolic blood pressure <60 mm Hg or a systolic blood pressure <90 mm Hg at the Screening or Day 1 Visit.
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- The subject has recent history (within the past 3 months) or current symptoms of orthostatic hypotension.
- Subject has a history of foot or toe amputation or an active foot or toe ulcer.
- 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.
- Subject has a history of substance abuse disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, within the past year, has current evidence of substance abuse disorder, is receiving medical treatment for drug abuse, or has a positive urine drug screen for a non-prescribed substance of abuse.
- Subject is receiving or has received within 30 days prior to the Screening Visit any prohibited medications or is anticipated to receive after the start of the trial any new prescription medication for their painful diabetic neuropathy. Subjects may be enrolled if stable on therapy for painful diabetic neuropathy.
- 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).
- Subject has estimated creatinine clearance less than 50 mL/min (Cockcroft Gault) at the Screening Visit.
- Subject has serum alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 times the upper limit of normal or total bilirubin concentrations >2.0 times the upper limit of normal at the Screening Visit.
- Subject has received an investigational drug within 30 days prior to the Screening Visit.
- Subject has been treated previously with clonidine topical gel or participated in a clonidine topical gel clinical study, including Study CLO 290.
- Subject is currently taking or has taken clonidine (any formulation) over the past 4 weeks.
- Subject has known hypersensitivity or intolerance to clonidine.
- Subject is receiving or has received ≤7 days prior to the start of the Screening Phase "alternative medicine" products or treatments (e.g., acupuncture, naturopathy, homeopathy, etc.) for management of pain.
- Subject has a history of malignancy within the past 5 years except for successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix.
- Subject is planning to have surgery during the course of the study.
- Subject has significant skin changes on physical examination associated with either pedal edema or venous stasis disease.
- Subject has any dermatologic condition of the lower extremities that could affect study drug absorption
- Subject has current symptoms of depression with a Beck Depression Inventory II (BDI II) score >19 at the Screening Visit.
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Study site
Anaheim, California, 92801
Study site
Belleville, Illinois, 62220
Study site
Blackfoot, Idaho, 83321
Study site
Blue Island, Illinois, 60406
Study site
Boise, Idaho, 83642
Study site
Chicago, Illinois, 60616
Study site
Cleveland, Ohio, 44122
Study site
Fort Myers, Florida, 33912
Study site
Glendale, Arizona, 85308
Study site
Hazelwood, Missouri, 63042
Study site
Houston, Texas, 77030
Study site
Knoxville, Tennessee, 37909
Study site
Norco, California, 92860
Study site
Ocala, Florida, 34471
Study site
Orlando, Florida, 32801
Study site
Phoenix, Arizona, 85018
Study site
Phoenix, Arizona, 85023
Study site
Sacramento, California, 95821
Study site
San Antonio, Texas, 78218
Study site
San Antonio, Texas, 78228
Study site
Santa Monica, California, 90404
Study site
Spartanburg, South Carolina, 29303
Study site
Tampa, Florida, 33634
Study site
Tustin, California, 92780
Study site
West Palm Beach, Florida, 33401
About this study
Official title: A Multicenter, Randomized, Double Blind, Parallel-Group Study Comparing the Efficacy and Safety of Clonidine Hydrochloride Topical Gel, 0.1%, to Clonidine Hydrochloride Gel Comparator in the Management of Painful Diabetic Neuropathy
The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who qualify to participate will apply study drug to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS) during the Treatment Phase for 12 weeks. Approximately 100 adult subjects will be randomized to receive Clonidine Gel or Clonidine Gel Comparator.
Read the detailed description
Study CLO-291 is a randomized, double-blind, comparator-controlled, parallel-group, multicenter study of 0.1% clonidine topical gel (Clonidine Gel) for the treatment of pain associated with painful diabetic neuropathy. The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who satisfy all eligibility criteria will apply Clonidine Gel Comparator to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS). Approximately 100 adult subjects will be randomized to receive Clonidine Gel or Clonidine Gel Comparator during the 12 week Treatment Phase.
- Conditions
- Painful Diabetic Neuropathy, Diabetic Neuropathy, Neuropathy
- Being tested
- Clonidine Hydrochloride Topical Gel, 0.1%, Clonidine Hydrochloride Gel Comparator
- 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 Hydrochloride Topical Gel, 0.1%Drug
Also called Clonidine Gel
Clonidine Gel is supplied as an aqueous gel formulation for topical use.
Clonidine Hydrochloride Gel ComparatorDrug
Also called Clonidine Gel Comparator
Clonidine Gel Comparator is supplied as an aqueous gel formulation for topical use.
| Study group | Role | What they receive |
|---|---|---|
| Clonidine Hydrochloride Topical Gel,0.1% | Experimental | Clonidine Hydrochloride Topical Gel,0.1% Receives: Drug: Clonidine Hydrochloride Topical Gel, 0.1% |
| Clonidine Hydrochloride Gel Comparator | Placebo comparator | Clonidine Hydrochloride Gel Comparator Receives: Drug: Clonidine Hydrochloride Gel Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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 (worse score from Day -14 to Day -8) to End-of-Treatment (worse score during Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "worse 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 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 (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.
- First posted31 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionNov 2016
- Study completionNov 2016
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 Painful Diabetic 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioDelivery Sciences International
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Aziz Shaibani, MD, Principal investigator, Nerve and Muscule Center of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02643251
- Sponsor's protocol ID
- CLO-291
- Status last verified
- Aug 2017
- First submitted
- 29 Dec 2015
- Last updated
- 20 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double Blind, Parallel-Group Study Comparing the Efficacy and Safety of Clonidine Hydrochloride Topical Gel, 0.1%, to Clonidine Hydrochloride Gel Comparator in the Management of Painful Diabetic Neuropathy
- ClinicalTrials.gov ID
- NCT02643251
- Acronym / sponsor ID
- CLO-291
- Conditions
- Painful Diabetic Neuropathy, Diabetic Neuropathy, Neuropathy
- Keywords
- Diabetes Mellitus, Pain, Foot Pain, Neuropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- BioDelivery Sciences InternationalIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 31 Dec 2015 (estimated)
- Results
- Posted 9 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who qualify to participate will apply study drug to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS) during the Treatment Phase for 12 weeks. Approximately 100 adult subjects will be randomized to receive Clonidine Gel or Clonidine Gel Comparator.
Detailed description
Study CLO-291 is a randomized, double-blind, comparator-controlled, parallel-group, multicenter study of 0.1% clonidine topical gel (Clonidine Gel) for the treatment of pain associated with painful diabetic neuropathy. The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who satisfy all eligibility criteria will apply Clonidine Gel Comparator to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS). Approximately 100 adult subjects will be randomized to receive Clonidine Gel or Clonidine Gel Comparator during the 12 week Treatment Phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clonidine Hydrochloride Topical Gel,0.1% | Experimental | Drug: Clonidine Hydrochloride Topical Gel, 0.1%Clonidine Hydrochloride Topical Gel,0.1% |
| Clonidine Hydrochloride Gel Comparator | Placebo comparator | Drug: Clonidine Hydrochloride Gel ComparatorClonidine Hydrochloride Gel Comparator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subject is fluent in English and has provided written informed consent.
- Subject is an outpatient ≥18 years of age at the time of the Screening Visit.
- Subject has Type 1 or Type 2 diabetes mellitus with a hemoglobin A1C value < 10% and has been stable on therapy (diet, oral anti-hyperglycemic, and/or insulin) for at least six (6) months prior to the Screening Visit.
- Subject is 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). A negative pregnancy test at the Screening and Day 1 visits is required for females of child-bearing potential. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
- Subject has chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for at least six (6) months. Pain should be clearly localized to the area of neuropathy (feet), and subjects should be able to distinguish the target pain from other painful areas and conditions.
Key exclusion criteria (24 listed)
- Subject has neuropathy secondary to non-diabetic causes in the opinion of the Investigator (e.g., vasculitis, familial neuropathy, alcoholism, pernicious anemia, hepatitis, malignancy, chronic inflammatory demyelinating polyneuropathy [CIDP], human immunodeficiency virus [HIV], medication-induced neuropathy, vitamin B12 deficiency).
- Subject has a significant neurological disorder or condition that might confound assessment of painful diabetic neuropathy (e.g., stroke with distal neurological deficit, mononeuritis multiplex, lumbar radiculopathy).
- Subject has a confounding disorder as determined by the Algorithm for Excluding Disorders that Masquerade as Painful Diabetic Neuropathy.
- Subject has other sustained pain with intensity at or greater than the bilateral neuropathic pain in the feet.
- Subject is using an implanted medical device (e.g., spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for treatment of pain.
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 |
|---|---|---|
| Clonidine Hydrochloride Topical Gel, 0.1%Also: Clonidine GelClonidine Gel is supplied as an aqueous gel formulation for topical use. | Drug | Clonidine Hydrochloride Topical Gel,0.1% |
| Clonidine Hydrochloride Gel ComparatorAlso: Clonidine Gel ComparatorClonidine Gel Comparator is supplied as an aqueous gel formulation for topical use. | Drug | Clonidine Hydrochloride Gel Comparator |
Primary outcome
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])
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.
1 secondary outcome
Mean Daily Worst Pain Intensity Numeric Pain Rating Scale Scores
Time frame: The change from Baseline (worse over Day -14 to Day -8) to End-of-Treatment (worse over Days 78 to 84 [±3 days])
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Aziz Shaibani, MD principal investigator
Nerve and Muscule Center of Texas
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clonidine Hydrochloride Topical Gel, 0.1% and Clonidine Hydrochloride Gel Comparator in people with Painful Diabetic Neuropathy and Diabetic Neuropathy, run by BioDelivery Sciences International at 25 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 11 inclusion and 24 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 20 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 25 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 9 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?
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 20 Sep 2017.