Extended-release Pregabalin for the Treatment of Neuropathic Pain in Patients With Diabetic Peripheral Neuropathy and Postherpetic Neuralgia

Official title

A Phase III, Multicenter, Randomized, Double-blind, Double-dummy, Controlled, Parallel-group, Non-inferiority Clinical Trial to Evaluate the Efficacy and Safety of Extended-release Pregabalin Tablets Compared With Immediate-release Pregabalin Tablets, in the Relief of Neuropathic Pain in Participants With Diabetic Peripheral Neuropathy or Postherpetic Neuralgia.

Overview

Extended-release Pregabalin for the Treatment of Neuropathic Pain in Patients With Diabetic Peripheral Neuropathy and Postherpetic Neuralgia

Interventions

• Drug Experimental: Pregabalin XR
  Pregabalin XR: extended-release tablet, with an initial dose of 82.5 mg once daily. The dose may be adjusted every 7 days during the first 4 weeks of treatment, up to a maximum of 660 mg once daily. In addition, the experimental group will receive a placebo twice daily.
• Drug Comparator: Dorene Tabs
  Pregabalin immediate-release tablets, at an initial dose of 75 mg twice daily. The dose may be adjusted every 7 days during the first 4 weeks of treatment, up to a maximum of 300 mg twice daily. In addition, the comparator group will receive a placebo once daily.
• Drug Comparator placebo
  Comparator placebo
• Drug experimental placebo
  experimental placebo

Primary outcome measures

• Difference in the mean pain intensity score 16 weeks after the start of treatment, compared to baseline [Time frame: 16 weeks]

Secondary outcome measures (5)

• To assess improvement in neuropathic pain during treatment. [Time frame: 1 to 12 weeks]
• To assess the proportion of participants who experienced significant improvement in neuropathic pain during and at the end of treatment. [Time frame: 1 to 16 weeks]
• To assess improvements in the impact of neuropathic pain on sleep, quality of life, and symptoms of anxiety and depression during and at the end of treatment. [Time frame: 1 to 16 weeks]
• Assess the participant's overall perception of change at the end of treatment. [Time frame: Week 16]
• Evaluate the use of rescue medication. [Time frame: 1 to 16 weeks.]

Eligibility criteria

Inclusion criteria

The following criteria must be met for a participant to be included in the study:

• Participants of either sex, aged 18 to 75 years.
• Be able to understand and agree to participate in the study, undergo the procedures, and attend the visits, as indicated by signing the informed consent form approved by the CEP/Conep System.
• Have a diagnosis of peripheral neuropathic pain associated with:

• diabetes mellitus (type 1 or 2), with glycated hemoglobin (HbA1c) levels ≤ 11%, documented symptoms of peripheral diabetic neuropathy for at least 6 months, and use of medication for glycemic control at a stable dose for at least 30 days.
• postherpetic neuralgia, with pain symptoms for at least 3 months following a skin rash due to an acute episode of herpes zoster.
• Presence of neuropathic pain, with an intensity of ≥ 4 on the 11-point DPRS numerical scale (from 0 "no pain" to 10 "worst possible pain"‡). ‡ Pain intensity ≥ 4 will be confirmed at the initial visit (IV); during the screening/randomization visit, Participant Diary No. 1 containing the DPRS scales will be provided, in which the participant will record pain intensity daily upon waking and at the end of the day for 7 days (±2 days). The mean value for pain intensity recorded during the Screening/Randomization Phase will be used to confirm eligibility at the initial visit (IV).
• Participants who are unable to become pregnant (postmenopausal women, defined as 12 months or more of amenorrhea, or who have undergone surgical sterilization\*; and men who have undergone vasectomy\*\*) OR participants of reproductive potential who agree to use a reliable method of contraception\*\*\*.

• Female sterilization (undergoing bilateral surgical oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks prior to administration of the investigational drug.

• Male sterilization at least 6 months prior to screening. \*\*\* If the participant is of childbearing age and decides to participate in the study, they must use or request that their partner use a safe contraceptive method. A safe contraceptive method is defined as the use of at least one of the following: condoms, a diaphragm, and/or a hormonal method (estrogenic and/or progestogenic) in the form of medication, including oral, vaginal, injectable, transdermal, and intrauterine devices. Only participants who expressly declare themselves exempt from the risk of pregnancy-whether because they do not engage in sexual activity or because they engage in it in a non-reproductive manner-will have the right to participate in the study without the mandatory use of contraceptives. Examples include participants who have undergone a vasectomy, those with an infertile partner, or those practicing total heterosexual abstinence.

The decision regarding the best contraceptive method to use will be made jointly by the physician and the study participant. If there are any costs involved, the chosen contraceptive method will be provided by the sponsor free of charge for as long as necessary. In addition, condoms with spermicide will be provided to participants at all study visits, when applicable.

Exclusion criteria

A positive response to any of the following criteria will exclude the participant from the study:

• The presence of pain unrelated to the primary diagnosis of diabetic peripheral neuropathy or postherpetic neuralgia that could interfere with the evaluation.
• Any skin condition that potentially alters sensation in the affected dermatome or area of neuropathic involvement, which could interfere with the assessment.
• Having undergone neurosurgical therapy for the treatment of neuropathy.
• Current use, or use within the past 7 days, of nerve block therapy and/or medications commonly used to treat neuropathic pain (e.g., benzodiazepines, skeletal muscle relaxants, capsaicin, local anesthetics, opioids, memantine), antiepileptic drugs (e.g., carbamazepine, clonazepam, phenytoin, valproic acid, lamotrigine, topiramate, gabapentin), antidepressants (e.g., tricyclics, serotonin reuptake inhibitors, venlafaxine), and potential neurotoxins (e.g., hydroxychloroquine, deferoxamine, thioridazine, vigabatrin).
• History of treatment failure or hypersensitivity to pregabalin or gabapentin.
• History of neoplastic disease within the past 2 years (excluding basal cell carcinoma), neurological disease, unstable heart disease, psychiatric conditions (particularly suicidal ideation), and/or infection with hepatitis B, hepatitis C, or HIV.
• Current laboratory abnormalities in liver enzymes (elevated AST and/or ALT 2.5 times the upper limit of the reference range) and/or renal insufficiency (glomerular filtration rate < 60 mL/min/1.73 m²).
• History of illicit drug abuse in the past 2 years.
• History of alcoholism (average alcohol intake exceeding 3 standard drinks\* per day or more than 7 standard drinks per week for women, and exceeding 4 standard drinks per day or more than 14 standard drinks per week for men) in the past 2 years.

\* A standard drink is: a can of regular beer (330 mL at 4%); a shot of distilled spirits (30 mL at 40%); a glass of wine or a small glass of sherry (100 mL at 12% or 70 mL at 18%); a small glass of liqueur or similar (50 mL at 25%) (53).

• Being pregnant, breastfeeding, or intending to become pregnant during the study period.
• Having participated in clinical studies in the past 12 (twelve) months, unless there may be a direct benefit to the study participant, at the investigator's discretion.
• Having any condition that prevents participation, at the investigator's discretion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Brazil · 15 centers

• Cpec Obras Sociais Irmã Dulce — Salvador
• Instituto Anima de Extensão Universitária - Unibh — Belo Horizonte
• Centro de Ensino Superior de Vespasiano — Vespasiano
• Instituto Estadual Do Cerebro Paulo Niemeyer — Rio de Janeiro
• Apec Sociedade Potiguar de Educação E Cultura — Natal
• Clinica Neurologica E Neurocirurgica de Joinville — Joinville
• Instituto Anima de Extensão Universitária - Unisul — Palhoça
• Fundação de Beneficência Hospital de Cirurgia — Aracaju
• … and 7 more centers

Identifiers

NCT: NCT07712913 · HYP008-24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗