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Completed

NCT Number: NCT01496365

Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

The purpose of this study is to evaluate the safety, tolerability and effectiveness of DS-5565 compared to placebo (inactive substance) and pregabalin in diabetic subjects with DPN.

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Key information

Conditions

Diabetic Peripheral Neuropathy Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Birmingham, Alabama, United States

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About this study

Diabetic peripheral neuropathy (DPN) affects up to 50% of patients who have diabetes for at least 25 years. Up to 26% of all patients with DPN experience neuropathic pain. DPN pain contributes to sleep disorders, depression, and anxiety, which together may have an impact on a patient's well-being and quality of life.

There are currently several drugs used to treat painful DPN. For example, Lyrica® (pregabalin) is approved by the United States Food and Drug Administration (FDA) to treat neuropathic pain associated with DPN and is commonly prescribed. The dosage of the FDA-approved drugs is limited by side-effects such as dizziness, sleepiness, weight gain and swelling of the hands, legs, and feet. As a result, many patients suffering from DPN pain do not get satisfactory pain relief.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age > 18 years of age
  • Able to give informed consent and willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
  • Type 1 or type 2 diabetes with a hemoglobin A1c (HbA1c) ≤ 10% at Screening and on a stable antidiabetic medication regimen for at least 30 days prior to Screening (insulin therapy is acceptable)
  • Painful distal symmetrical sensorimotor polyneuropathy (as per American Society of Pain Educators guidelines ) diagnosed for at least 6 months, based on neurological history and/or examination; diagnosis includes absent or reduced deep tendon reflexes at both ankles
  • At Screening, a pain score of ≥ 40 mm on the SF-MPQ VAS
  • At Randomization, a pain score of ≥ 40 mm on the SF-MPQ VAS and an ADPS of ≥ 4 on the 11-point NRS, the latter calculated from a minimum of 4 pain ratings in daily diaries obtained during the 1-week Baseline Period (prior to randomization)
  • Creatinine clearance > 60 mL/min (estimated using the Cockcroft-Gault equation)
  • Antidiabetic and other medications anticipated to remain stable and constant during the study period
  • Women of child bearing potential (WOCBP) must be using an adequate method of contraception as detailed in the protocol to avoid pregnancy during the study and for 4 weeks after study completion

Exclusion criteria

  • Diagnosis of mononeuropathy
  • Use of concomitant medications that may confound assessments of efficacy and/or safety (see Section 5.2)
  • Major psychiatric disorders
  • Have had a malignancy other than basal cell carcinoma within the past 2 years
  • At Visit 1, have a white blood cell count < 2500/mm3, neutrophil count < 1500/mm3, or platelet count < 100 x 103/mm3
  • Clinically significant unstable diabetes mellitus, unstable hepatic, respiratory, or hematologic illness, unstable cardiovascular disease (including myocardial infarction in the 3 months prior to Visit 1), or symptomatic peripheral vascular disease
  • Clinically significant findings on the Screening ECG
  • History of pernicious anemia, untreated hypothyroidism, chronic hepatitis B, hepatitis B within the past 3 months, or human immunodeficiency virus infection
  • Amputations of body parts other than toes
  • Prior therapeutic failure of pregabalin or gabapentin (considered unresponsive or intolerant to treatment); therapeutic failure implies lack of efficacy following full titration to effective doses (eg, 300 mg/day for pregabalin)
  • Known hypersensitivity to pregabalin or gabapentin
  • Requirement for concomitant anticonvulsant and antidepressant therapy, with the exception of stable doses of SSRIs
  • Neurologic disorders unrelated to DPN that may confound the assessment of pain associated with DPN
  • Skin conditions that could alter sensation
  • Other sources of pain that may confound assessment or self-evaluation of the pain due to DPN
  • Abuse of prescription medications, street drugs or alcohol (including alcohol dependence) within the last 1 year
  • Current enrollment in another investigational study, participation in another investigational study with the past 30 days, or other current or recent use of any investigational drug
  • Pregnancy (as based on lab test results) or breast feeding
  • Laboratory values exceeding limits listed in Table 4.1 of the protocol

Treatment and study plan

DS-5565 tablet

Drug

5mg and 10mg tablets

Pregabalin capsule

Drug

75mg and 150mg over-encapsulated

Other names: Lyrica

Placebo Tablet

Drug

Other names: placebo tablet matching DS-5565 tablet

Placebo capsule

Drug

Other names: placebo capsule matching over-encapsulated pregabalin

Primary outcomes

  1. Mean Change From Baseline to Week 5 in Average Daily Pain Score (ADPS) Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    Average daily pain score (ADPS) is a participant-reported instrument that measures pain intensity using an 11-point numeric rating scale (NRS) where 0 is defined as no pain and 10 is defined as worst possible pain. Higher scores indicate worse pain intensity level. The change from baseline to Week 5 is reported where a negative value is considered an improvement in pain intensity. A minimally meaningful effect was defined as a decrease of at least 1.0 point [scale of 0 to 10] versus placebo).

Secondary outcomes

  1. Least Square Means of Average Daily Pain Score by Week Mixed Effects Model for Repeated Measures (MMRM) Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    Average daily pain score (ADPS) is a participant-reported instrument that measures pain intensity using an 11-point numeric rating scale (NRS) where 0 is defined as no pain and 10 is defined as worst possible pain. Higher scores indicate worse pain intensity level. The least square means of ADPS (assessed by MMRM) are reported where a negative value is considered an improvement in pain intensity. A minimally meaningful effect was defined as a decrease of at least 1.0 point [scale of 0 to 10] versus placebo).

  2. Average Daily Pain Score Responder Rates Based on ≥30% and ≥50% Decrease From Baseline at Endpoint) Following Treatment With DS-5565 or Placebo Compared to Pregabalin

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    Average daily pain score (ADPS) is a participant-reported instrument that measures pain intensity using an 11-point numeric rating scale (NRS) where 0 is defined as no pain and 10 is defined as worst possible pain. Higher scores indicate worse pain intensity level.

  3. Mean Change From Baseline to End-of-Treatment in Average Daily Sleep Interference Score Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    Average Daily Sleep Interference Score (ADSIS) is the weekly average of patient-reported sleep interference (rated every morning on a numerical scale of 0 = "pain did not interfere with sleep" to 10 = "pain completely interfered with sleep" over the past 24 h), where higher scores indicate worse outcome.The change from baseline to Week 5 in ADSIS is being reported as the average of the last 7 available daily scores. The greater the negative value, the greater the improvement in sleep.

  4. Short-Form McGill Pain Questionnaire (SF-MPQ) Sensory and Affective Scores Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The SF-MPQ sensory score is the sum of 11 pain descriptors each scored from 0 to 3:

    throbbing, shooting, stabbing, sharp cramping, gnawing, hot-burning, aching, heavy, tender, and splitting. Thus, the SF-MPQ sensory score ranges from 0 to 33, where lower scores indicate a better outcome. The SF-MPQ affective score is the sum of four pain descriptors each scored from 0 to 3: tiring-exhausting, sickening, fearful, and punishing cruel. Thus, SF-MPQ affective score ranges from 0 to 12, where lower scores indicate a better outcome. The change from baseline to Week 5 in SF-MPQ sensory and affective scores are being reported. The greater the negative value, the greater the improvement in sensory and affective scores.

  5. Short-Form McGill Pain Questionnaire (SF-MPQ) Total Score and Visual Analog Scale Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The SF-MPQ sensory score is the sum of 11 pain descriptors each scored from 0 to 3: throbbing, shooting, stabbing, sharp cramping, gnawing, hot-burning, aching, heavy, tender, and splitting. Thus, the SF-MPQ sensory score ranges from 0 to 33, where lower scores indicate a better outcome. The SF-MPQ affective score is the sum of four pain descriptors each scored from 0 to 3: tiring-exhausting, sickening, fearful, and punishing cruel. Thus, SF-MPQ affective score ranges from 0 to 12, where lower scores indicate a better outcome. The SF-MPQ total score comprises the sum of the sensory and affective scores. The SF-MPQ VAS ranges from 0 (no pain) to 100 (worst possible pain), where lower scores indicate a better outcome. The change from baseline to Week 5 in SF-MPQ total score and VAS are being reported. The greater the negative value, the greater the improvement in total score (sensory and affective scores) and VAS pain.

  6. Short-Form McGill Pain Questionnaire (SF-MPQ) Present Pain Intensity Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The SF-MPQ present pain intensity ranges from 0 (no pain) to 5 (excruciating), where lower scores indicate a better outcome. The change from baseline to Week 5 in SF-MPQ present pain intensity is being reported. The greater the negative value, the greater the improvement in present pain intensity.

  7. Mean Change From Baseline to Endpoint of Modified Brief Pain Inventory (BPI) Subscale, Interference With Daily Functions, Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The Modified Brief Pain Inventory (BPI) includes Interference with Daily Functions Subscale, Worst Pain Intensity, Least Pain Intensity, Average Pain Intensity, Pain Right Now, and Relief From Pain. The range of interference subscale is 0-10, where lower scores indicate a better outcome. The change from baseline to Week 5 in Modified Brief Pain Inventory is being reported. The greater the negative value, the greater the improvement in interference with daily functions.

  8. Mean Change From Baseline to Endpoint of Modified BPI Subscales, Worst, Least and Average Pain Intensity, Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The Modified Brief Pain Inventory (BPI) includes Interference with Daily Functions Subscale, Worst Pain Intensity, Least Pain Intensity, Average Pain Intensity, Pain Right Now, and Relief From Pain. The range of worst pain intensity in the last 24 hours is 0-10, where lower scores indicate a better outcome. The range of least pain intensity in the last 24 hours is 0-10, where lower scores indicate a better outcome. The range of average pain intensity in the last 24 hours is 0-10, where lower scores indicate a better outcome. The change from baseline to Week 5 in Modified Brief Pain Inventory is being reported. The greater the negative value, the greater the improvement in worst, least, and average pain intensity.

  9. Mean Change From Baseline to Endpoint of Modified BPI Subscale, Pain Right Now, Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The Modified Brief Pain Inventory (BPI) includes Interference with Daily Functions Subscale, Worst Pain Intensity, Least Pain Intensity, Average Pain Intensity, Pain Right Now, and Relief From Pain. The range of pain right now is 0-10, where lower scores indicate a better outcome. The change from baseline to Week 5 in Modified Brief Pain Inventory is being reported. For pain right now, the greater the negative value, the greater the improvement.

  10. Mean Change From Baseline to Endpoint of Modified BPI Subscale, Relief From Pain, Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    The Modified Brief Pain Inventory (BPI) includes Interference with Daily Functions Subscale, Worst Pain Intensity, Least Pain Intensity, Average Pain Intensity, Pain Right Now, and Relief From Pain. The range of % relief from pain is 0-100, where higher scores indicate a better outcome. The change from baseline to Week 5 in Modified Brief Pain Inventory is being reported. For relief from pain, the higher the score, the greater the improvement in pain relief.

  11. Patient Global Impression of Change at End-of-Treatment or Early Termination Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: Baseline up to Week 5 postdose, up to 10 months total follow up

    Patient Global Impression of Change (PGIC) has a range of 7 possible responses for overall status since start of the study, where 0 was defined as 'Very much improved' and 7 was defined as 'Very much worse'. Lower scores indicate a better outcome. PGIC was analyzed based on the following definitions: Participant's overall status was minimally improved or better (ie, score ≤3) or Participant's overall status was much improved or better (ie, score ≤ 2).

  12. Drug-related Treatment-Emergent Adverse Events (n ≥2 Participants in Any Treatment Group) Following Treatment With DS-5565 Compared to Pregabalin and Placebo

    Time frame: From the time of signing the informed consent form (ICF) up to 10 months postdose

    Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) which began or worsened in severity after the first administration of study drug. Drug-related TEAEs included AEs that were considered related to the study drug as judged by the Investigator. TEAEs were classified according to MedDRA 14.1.

Sponsors and collaborators

Lead sponsor

Daiichi Sankyo

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo and Active Comparator-Controlled Study of DS-5565 for Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Dec 21, 2011
Registry last updated
Jan 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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