A Study to Evaluate Pregabalin in Painful Diabetic Peripheral Neuropathy

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Pregabalin Sustained-Release Tablets for the Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

This study is designed to evaluate the efficacy and safety of pregabalin extended-release tablets in the treatment of neuropathic pain associated with diabetic peripheral neuropathy. Pregabalin has been approved in more than 130 countries for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and neuralgia associated with spinal cord injury. Pregabalin extended-release tablets were administered once daily, as a single dose after dinner. Compared with pregabalin capsule formulation, it reduces the frequency of medication and improves patient compliance.

Study Overview

• Status: Not yet recruiting
• Conditions: Painful Diabetic Neuropathy
• Intervention / Treatment: Drug: pregabalin sustained-release tablets; Drug: Placebo

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled trial, the study was designed to evaluate the efficacy and safety of pregabalin sustained-release tablets in the treatment of neuropathic pain associated with diabetic peripheral neuropathy. The study includes a screening period (3 weeks, including baseline/run-in period), a treatment period (titration period, fixed dose period and withdrawal period), and a follow-up period. During the treatment period participants will receive pregabalin sustained-release tablets/placebo as daily treatment.

• Study Type: Interventional
• Enrollment (Estimated): 358
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥ 18 years and ≤ 75 years at screening;
• diagnosed with type 1 or type 2 diabetes for ≥ 1 year;
• diagnosed with distal symmetrical polyneuropathy caused by diabetes (type 1 or type 2), with duration of neuropathic pain associated with diabetic peripheral neuropathy ≥ 6 months;
• clearly understood and voluntarily participated in the study, and signed the informed consent form by themselves.

Exclusion Criteria:

• Subjects with other conditions that may confound the assessment of Neuropathic Pain associated with Diabetic Peripheral neuropathy (DPNP), such as: neuropathic pain other than DPNP (cervical spondylosis, carpal tunnel syndrome, spinal stenosis, postherpetic pain, etc.), pain caused by other causes (gout, chronic obstructive arteriosclerosis, arthritis, etc.), and other pain at the assessment site (skin diseases and trauma);
• subjects with known or suspected allergic reactions to various components of pregabalin sustained-release tablets or compounds closely related to paracetamol or paracetamol;
• subjects with clinically significant or unstable diseases, such as but not limited to severe cardiovascular disease, cerebrovascular disease, liver, kidney, respiratory system, blood system, immune system diseases, inflammatory or rheumatic diseases, uncontrolled infection, untreated endocrine diseases, etc., and other conditions that judged by the investigator to influence participation in the trial;
• subjects who have undergone renal transplantation, or are undergoing renal dialysis;
• subjects with uncontrolled narrow-angle glaucoma, uncontrolled seizure history, or uncontrolled or poorly controlled hypertension;
• Pregnant or lactating females or subjects planning to father a child during the trial (including males);
• subjects with a history of drug or alcohol abuse within one year prior to screening; patients who, in the opinion of the investigator, are not suitable for participation in this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator	Drug: Placebo; Subjects will take placebo tablets for the duration of 14 weeks. The dosage will include 165 mg daily (for the titration and the withdraw period) and 330 mg daily for the fixed-dose period.
Experimental: Experimental: pregabalin sustained-release tablets	Drug: pregabalin sustained-release tablets; Subjects will take pregabalin sustained-release tablets for the duration of 14 weeks. The dosage will include 165 mg daily (for the titration and the withdraw period) and 330 mg daily for the fixed-dose period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale (NRS) mean change at week 13.	The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. Change from baseline in weekly mean of NRS (numeric rating scale) at week 13 will be recorded	Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS mean change at Weeks 1-12 and 14	The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. Change from baseline in weekly mean NRS pain score at Weeks 1-12 and 14 during the treatment period will be recorded;	Weeks 1-12 and 14
Proportion of subjects with NRS change	The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. Proportion of subjects with ≥ 50% and ≥ 30% change from baseline in weekly mean NRS pain score at Week 13 will be recorded;	Week 13
Brief McGill Pain Questionnaire (SF-MPQ) score	It is a self-report questionnaire that allows individuals to give their doctor a good description of the quality and intensity of pain that they are experiencing. Users first select a single word from each group that best reflects their pain; then respondents specify their level of pain by indicating a position along a continuous line between two end-points; then subjects chose the numer best represent their current pain intensity (0~5). Change from baseline in SF-MPQ (Brief McGill Pain Questionnaire) total score and each subscale Pain Grading Index (PRI), Visual Analogue Scale (VAS), and Present Pain Intensity (PPI) scores at Weeks 1, 5, 9, 13, and 14 after treatment;	Weeks 1, 5, 9, 13, and 14
Medical Outcomes Study Sleep Scale (MOS-SS) score	Participants answered a series of 12 questions assessing sleep, with values ranging from 1 to 6, and an additional dichotomous indicator of optimal sleep. All items are scored so that a high score reflects more of the attribute implied by the scale name. Each item is then converted to a 0 to 100 possible range so that the lowest and highest possible scores are set at 0 and 100, respectively. In this format, scores represent the achieved percentage of the total possible score. Change from baseline in MOS-SS sleep scale score and each subscale (sleep interference, sleep adequacy, daytime mental status, snoring, shortness of breath upon awakening, and sleep volume) score at Weeks 1, 5, 9, 13, and 14 after treatment;	Weeks 1, 5, 9, 13, and 14
Hospital Anxiety and Depression Scale (HADS) score	The HADS is a fourteen-item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Change from baseline in HADS (Hospital Anxiety and Depression Scale) score at Weeks 1, 5, 9, 13, and 14 after treatment;	Weeks 1, 5, 9, 13, and 14
Patient Global Impression of Improvement (PGIC) score	The Patient Global Impression of Change (PGIC) is a patient-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse"). The PGIC is based on the validated Clinical Global Impression of Change scale. Change from baseline in PGIC (Patient Global Impression of Improvement) score at Weeks 1, 5, 9, 13, 14 after treatment will be recorded;	Weeks 1, 5, 9, 13, and 14
Clinical Global Impression of Improvement (CGIC) score	The Clinical Global Impression of Change (PGIC) is a clinician-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse"). Change from baseline in CGIC (Clinical Global Impression of Improvement) score at Weeks 1, 5, 9, 13, 14 after treatment;	Weeks 1, 5, 9, 13, and 14

Collaborators and Investigators

• Sponsor: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 15, 2025

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain; 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: HEX1939-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No