Randomized, Double-Blind, Multicenter, Placebo-Controlled Study Of Pregabalin For Pain Associated With Diabetic Peripheral Neuropathy

Randomized, Double-Blind, Multicenter, Placebo-Controlled Study To Evaluate Efficacy And Safety Of Pregabalin (CI-1008) In The Treatment For Pain Associated With Diabetic Peripheral Neuropathy

To evaluate the efficacy and safety of pregabalin at 300 mg/day and 600 mg/day (BID) in patients with painful diabetic peripheral neuropathy.

Study Overview

• Status: Completed
• Conditions: Diabetic Neuropathy, Painful
• Intervention / Treatment: Drug: placebo; Drug: pregabalin; Drug: pregabalin

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Pfizer Investigational Site
  • Kumamoto, Japan
    • Pfizer Investigational Site
  • Nagasaki, Japan
    • Pfizer Investigational Site
  • Niigata, Japan
    • Pfizer Investigational Site
  • Oita, Japan
    • Pfizer Investigational Site
  • Okayama, Japan
    • Pfizer Investigational Site
  • Saga, Japan
    • Pfizer Investigational Site
  • Saitama, Japan
    • Pfizer Investigational Site
  • Tokushima, Japan
    • Pfizer Investigational Site
  • Aichi
    • Nagoya, Aichi, Japan
      • Pfizer Investigational Site
  • Fukuoka
    • Chikushino, Fukuoka, Japan
      • Pfizer Investigational Site
    • Kasuga, Fukuoka, Japan
      • Pfizer Investigational Site
  • Fukushima
    • Date-shi, Fukushima, Japan
      • Pfizer Investigational Site
    • Nihonmatsu, Fukushima, Japan
      • Pfizer Investigational Site
    • Shirakawa-shi, Fukushima, Japan
      • Pfizer Investigational Site
    • Sukagawa, Fukushima, Japan
      • Pfizer Investigational Site
  • Hiroshima
    • Kure, Hiroshima, Japan
      • Pfizer Investigational Site
  • Hokkaido
    • Chitose, Hokkaido, Japan
      • Pfizer Investigational Site
    • Ebetu, Hokkaido, Japan
      • Pfizer Investigational Site
    • Sapporo, Hokkaido, Japan
      • Pfizer Investigational Site
  • Hokkaiido
    • Sapporo, Hokkaiido, Japan
      • Pfizer Investigational Site
  • Hyogo
    • Kobe, Hyogo, Japan
      • Pfizer Investigational Site
  • Ibaraki
    • Inashiki, Ibaraki, Japan
      • Pfizer Investigational Site
  • Kanagawa
    • Kamakura, Kanagawa, Japan
      • Pfizer Investigational Site
    • Yokohama, Kanagawa, Japan
      • Pfizer Investigational Site
  • Kumamoto
    • Yatsushiro, Kumamoto, Japan
      • Pfizer Investigational Site
  • Miyagi
    • Sendai, Miyagi, Japan
      • Pfizer Investigational Site
  • Nagano
    • Matsumoto, Nagano, Japan
      • Pfizer Investigational Site
    • Ueda, Nagano, Japan
      • Pfizer Investigational Site
  • Oita
    • Beppu, Oita, Japan
      • Pfizer Investigational Site
  • Okayama
    • Yamada, Okayama, Japan
      • Pfizer Investigational Site
  • Okinawa
    • Naha, Okinawa, Japan
      • Pfizer Investigational Site
    • Tomishiro, Okinawa, Japan
      • Pfizer Investigational Site
    • Urazoe, Okinawa, Japan
      • Pfizer Investigational Site
  • Osaka
    • Higashiosaka, Osaka, Japan
      • Pfizer Investigational Site
    • Hirano-ku, Osaka, Japan
      • Pfizer Investigational Site
    • Kishiwada, Osaka, Japan
      • Pfizer Investigational Site
    • Suminoe-ku, Osaka, Japan
      • Pfizer Investigational Site
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan
      • Pfizer Investigational Site
  • Tochigi
    • Oyama-shi, Tochigi, Japan
      • Pfizer Investigational Site
    • Utsunomiya, Tochigi, Japan
      • Pfizer Investigational Site
  • Tokyo
    • Arakawa, Tokyo, Japan
      • Pfizer Investigational Site
    • Bunkyo-ku, Tokyo, Japan
      • Pfizer Investigational Site
    • Chiyoda-ku, Tokyo, Japan
      • Pfizer Investigational Site
    • Chuo-ku, Tokyo, Japan
      • Pfizer Investigational Site
    • Minato-ku, Tokyo, Japan
      • Pfizer Investigational Site
    • Nishitokyo, Tokyo, Japan
      • Pfizer Investigational Site
    • Ohta-ku, Tokyo, Japan
      • Pfizer Investigational Site
    • Shibuya-ku, Tokyo, Japan
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Visual Analogue Scale (VAS) of pain is higher than 40 mm.
• Diagnosis of type 1 or 2 diabetes mellitus for at least 1 year

Exclusion Criteria:

• Malignancy within the past 2 years.
• Neurologic disorders unrelated to diabetic neuropathy that may confuse the assessment of neuropathy pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; Dosage: placebo, oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose)
Experimental: Pregabalin 300 mg/day	Drug: pregabalin; Dosage: 300 mg/day (150 mg bid), oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose); Drug: pregabalin; Dosage: 600 mg/day (300 mg bid), oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose)
Experimental: Pregabalin 600 mg/day	Drug: pregabalin; Dosage: 300 mg/day (150 mg bid), oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose); Drug: pregabalin; Dosage: 600 mg/day (300 mg bid), oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Study Endpoint in Mean Weekly Pain Scores	Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline to Study Endpoint in Mean Weekly Pain Scores by Groups of Subjects With Expected Similar Plasma Concentrations	Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose. Subjects are classified by exposure to pregabalin, which is estimated by creatinine clearance (CLcr).	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Number of Responders	A responder is defined as a subject with a 50% reduction in weekly mean pain score from baseline to study endpoint.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline at Week 1 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 1. Change from baseline: Score at Week 1 minus score at baseline	From baseline to Week 1
Change From Baseline at Week 2 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 2. Change from baseline: Score at Week 2 minus score at baseline	From baseline to Week 2
Change From Baseline at Week 3 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 3. Change from baseline: Score at Week 3 minus score at baseline	From baseline to Week 3
Change From Baseline at Week 4 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 4. Change from baseline: Score at Week 4 minus score at baseline	From baseline to Week 4
Change From Baseline at Week 5 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 5. Change from baseline: Score at Week 5 minus score at baseline	From baseline to Week 5
Change From Baseline at Week 6 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 6. Change from baseline: Score at Week 6 minus score at baseline	From baseline to Week 6
Change From Baseline at Week 7 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 7. Change from baseline: Score at Week 7 minus score at baseline	From baseline to Week 7
Change From Baseline at Week 8 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 8. Change from baseline: Score at Week 8 minus score at baseline	From baseline to Week 8
Change From Baseline at Week 9 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 9. Change from baseline: Score at Week 9 minus score at baseline	From baseline to Week 9
Change From Baseline at Week 10 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 10. Change from baseline: Score at Week 10 minus score at baseline	From baseline to Week 10
Change From Baseline at Week 11 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 11. Change from baseline: Score at Week 11 minus score at baseline	From baseline to Week 11
Change From Baseline at Week 12 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 12. Change from baseline: Score at Week 12 minus score at baseline	From baseline to Week 12
Change From Baseline at Week 13 in Mean Weekly Pain Scores	The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 13. Change from baseline: Score at Week 13 minus score at baseline	From baseline to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Physical Functioning	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Role Limitations-Physical	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Bodily Pain	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: General Health Perception	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Social Functioning	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Role Limitations-Emotional	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Vitality	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Mental Health	The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Mean Sleep Interference Scores	The mean change from baseline in the weekly mean sleep interference score at study endpoint. Score range is from 0-10. Higher scores indicate more severe interference with sleep.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short-Form McGill Pain Questionnaire: Sensory Scores	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Sensory score ranges from 0-33. Higher scores indicate more severe pain.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short-Form McGill Pain Questionnaire: Affective Scores	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Affective score ranges from 0-12. Higher scores indicate more severe pain.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short-Form McGill Pain Questionnaire: Total Scores	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Total score ranges from 0-45. Higher scores indicate more severe pain.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short-Form McGill Pain Questionnaire: Visual Analogue Scale Scores	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Visual Analogue Scale Score ranges from 0-100 mm. Higher scores indicate more severe pain.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Short-Form McGill Pain Questionnaire: Present Pain Intensity Scores	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Present pain intensity score ranges from 0-5. Higher scores indicate more severe pain.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Disturbance	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep disturbance ranges from 0-100. Higher scores indicate more severe pain.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Snoring	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for snoring ranges from 0-100. Higher scores indicate more of the attribute.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Shortness of Breath or Headache	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep shortness of breath or headache ranges from 0-100. Higher scores indicate more of the attribute.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Quantity of Sleep	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for quantity of sleep ranges from 0-24. Higher scores indicate more of the attribute named in the subscale.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Adequacy	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep adequacy ranges from 0-100. Higher scores indicate more of the attribute.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Somnolence	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for somnolence ranges from 0-100. Higher scores indicate more of the attribute.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Overall Sleep Problems Index	The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for overall sleep problems index ranges from 0-100. Higher scores indicate more of the attribute.	From baseline to Week 13 or up to study discontinuation (Study Endpoint)
Clinical Global Impression of Change	Clinical Global Impression of Change is a clinician-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).	Week 13 or up to discontinuation
Patient Global Impression of Change	The Patient Global Impression of Change is a patient-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).	Week 13 or up to discontinuation

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Alexander J Jr, Edwards RA, Manca L, Grugni R, Bonfanti G, Emir B, Whalen E, Watt S, Brodsky M, Parsons B. Integrating Machine Learning With Microsimulation to Classify Hypothetical, Novel Patients for Predicting Pregabalin Treatment Response Based on Observational and Randomized Data in Patients With Painful Diabetic Peripheral Neuropathy. Pragmat Obs Res. 2019 Oct 31;10:67-76. doi: 10.2147/POR.S214412. eCollection 2019.
• Alexander J Jr, Edwards RA, Brodsky M, Manca L, Grugni R, Savoldelli A, Bonfanti G, Emir B, Whalen E, Watt S, Parsons B. Using time series analysis approaches for improved prediction of pain outcomes in subgroups of patients with painful diabetic peripheral neuropathy. PLoS One. 2018 Dec 6;13(12):e0207120. doi: 10.1371/journal.pone.0207120. eCollection 2018. Erratum In: PLoS One. 2019 Feb 26;14(2):e0212959.
• Edwards RA, Bonfanti G, Grugni R, Manca L, Parsons B, Alexander J. Predicting Responses to Pregabalin for Painful Diabetic Peripheral Neuropathy Based on Trajectory-Focused Patient Profiles Derived from the First 4 Weeks of Treatment. Adv Ther. 2018 Oct;35(10):1585-1597. doi: 10.1007/s12325-018-0780-3. Epub 2018 Sep 11.
• Parsons B, Li C, Emir B, Vinik AI. The efficacy of pregabalin for treating pain associated with diabetic peripheral neuropathy in subjects with type 1 or type 2 diabetes mellitus. Curr Med Res Opin. 2018 Nov;34(11):2015-2022. doi: 10.1080/03007995.2018.1509304. Epub 2018 Sep 20.
• Markman JD, Jensen TS, Semel D, Li C, Parsons B, Behar R, Sadosky AB. Effects of Pregabalin in Patients with Neuropathic Pain Previously Treated with Gabapentin: A Pooled Analysis of Parallel-Group, Randomized, Placebo-controlled Clinical Trials. Pain Pract. 2017 Jul;17(6):718-728. doi: 10.1111/papr.12516. Epub 2016 Dec 1.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: November 2, 2007
• First Submitted That Met QC Criteria: November 2, 2007
• First Posted (Estimate): November 4, 2007

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetic Neuropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081163