Efficacy of Pregabalin and Duloxetine in Patients With PDPN: the Effect of Pain on Cognitive Function, Sleep and Quality of Life

NCT04246619 | Terminated Phase 4

• 2 other identifiers: KCT 11/20172017-004341-24
• Study Type: interventional
• Target: 254
• Locations: 5 countries
• Sites: 13

Brief Summary

The objective and the purpose of the trial is to: assess the efficacy of Pregabalin Krka and Dulsevia® in patients with PDPN, investigate the effect of Pregabalin Krka and Dulsevia® on pain and on quality of life (QOL), depression symptoms, cognitive functions, sleep quality and daytime sleepiness and assess the safety of Pregabalin Krka and Dulsevia® in patients with PDPN. During the 3 months (12 weeks) 5 visits and 2 phone calls are planned. After the ICF signature and before therapy is allocated, a screening procedure is carried out to verify eligibility: laboratory analyses (concentrations of TSH, vitamin B12, folic acid, glucose, HbA1c, pregnancy test for women of childbearing potential), assessment of PDPN (with questionnaire DN4), assessment of cognition (with questionnaire MoCA), habits, medical history (medical/surgical history and concomitant diseases, previous and/or existing therapy of pain in PDPN, concomitant medications) with measurements and evaluation of pain according to VAS. On Visit 2 investigator checks the results of laboratory tests, of pregnancy test, measures vital signs, evaluates pain in PDPN according to VAS, checks previous analgesic therapy and concomitant medications. If patient meets all inclusion and exclusion criteria, he/she is eligible and will be randomly assigned (automatically through electronic version of case report form (eCRF) into two therapy groups (treatment arms) - tretament with Pregabalin Krka OR treatment with Dulsevia®. Investigator performs assessments of: QoL, sleep quality and daytime sleepiness, depression and adverse events. At Visit 3, compliance monitoring is done, pain intensity in PDPN by VAS is evaluated, concomitant therapy is checked, vital signs are measured, doses of IMP are adjusted and adverse events assessment are carried out. At Visit 4, pregnancy test for women of childbearing potential and compliance monitoring are carried out; concomitant medications are checked, vital signs are measured, pain intensity in PDPN by VAS is evaluated, IMP are adjusted and assessment of adverse events is carried out. At Visit 5 investigator performs again assessments of: QoL, sleep quality and daytime sleepiness, depression, cognition and PDPN. Evaluation of the pain intensity in PDPN by VAS and assessment of the adverse events should be performed. Pregnancy test for women of childbearing potential is carried out.

Conditions

Painful Diabetic Peripheral Neuropathy

Outcome Measures

Primary Outcomes (2)

• Clinically meaningful improvement of pain in PDPN after a 12 week treatment with pregabalin

  Clinically meaningful improvement of pain in PDPN after a 12 week treatment according to VAS

  12 weeks

• Clinically meaningful improvement of pain in PDPN after a 12 week treatment with duloxetine

  Clinically meaningful improvement of pain in PDPN after a 12 week treatment according to VAS

  12 weeks

Secondary Outcomes (16)

• The proportion of patients with reduction of pain in PDPN for equal or more than 30 % AND/OR with pain intensity in PDPN not exceeding 30 mm

  week 1, week 2, week 6, week 8

• The proportion of patients with reduction of pain in PDPN for equal or more than 30 % AND/OR with pain intensity in PDPN not exceeding 30 mm

  week 8, week 12

• Pain intensity difference in PDPN

  week 1, week 2, week 6, week 8, week 12

• Pain intensity difference in PDPN

  week 8, week 12

• The proportion of patients with reduction of pain in PDPN for equal or more than 50 %

  Baseline vs.: week 1, week 2, week 6, week 8, week 12

Study Arms (2)

Pregabalin Krka Arm

EXPERIMENTAL

ARM 1: pregabalin (Pregabalin Krka 25-150 mg/ day) FLEXIBLE-DOSE REGIMEN. Investigator can choose on V2: * Total Pregabalin Krka daily dose: 25 mg/day * Total Pregabalin Krka daily dose: 50 mg/day * Total Pregabalin Krka daily dose: 75 mg/day * Total Pregabalin Krka daily dose: 150 mg/day * Total Pregabalin Krka daily dose: 300 mg/day (from Phone call 1 further on) V3: daily dose should be achieved: MINIMUM dose 150 mg/day Investigator can choose: total Pregabalin Krka daily dose 150 mg/day or 300 mg/day or 600 mg/day Investigator can choose: total Pregabalin Krka daily dose 150 mg/day or 300 mg/day or 600 mg/day V4: Investigator can choose: total Pregabalin Krka daily dose 150 mg/day or 300 mg/day or 600 mg/day

Drug: Pregabalin

Dulsevia® Arm

EXPERIMENTAL

• ARM 2: duloxetine (Dulsevia® 30-60 mg/ day) FLEXIBLE-DOSE REGIMEN: Investigator can choose on V2: * Total Dulsevia® daily dose: 30 mg/day * Total Dulsevia® daily dose: 60 mg/day V3: daily dose should be achieved: MINIMUM dose 60 mg/day Investigator can choose total Dulsevia® daily dose 60 mg/day or 90 mg/day or 120 mg/day. V4: Investigator can choose total Dulsevia® daily dose 60 mg/day or 90 mg/day or 120 mg/day.

Drug: Duloxetine

Interventions

Pregabalin DRUG

Pregabalin Krka (pregabalin) hard capsules of different strenghts: 25 mg, 75 mg, 150 mg, 300 mg. Duration: 12 weeks

Pregabalin Krka Arm

Duloxetine DRUG

Dulsevia® (duloxetine) hard gastro-resistant capsules of different strenghts: 30 mg and 60 mg. Duration: 12 weeks

Dulsevia® Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male patients aged 18-85 years.
• Patients with a history of type 2 diabetes mellitus according to The American Diabetes Association (ADA).
• Patients with a diagnosis of painful diabetic peripheral neuropathy (PDPN) caused by type 2 diabetes mellitus based on DN4 ≥4.
• Patients whose average pain intensity in PDPN in last 24 hours (measured by VAS), evaluated on baseline visit, is equal or more than 40 mm (0 mm ='no pain' and 100 mm ='worst possible pain').
• Ability to adhere to trial protocol.
• Written informed consent.

You may not qualify if:

• Patients who took PDPN medication and/or analgesics on a day of baseline visit.
• Patients with a known hypersensitivity to duloxetine, pregabalin, paracetamol or tramadol or any of the inactive ingredients or have any contraindication for the use of duloxetine, pregabalin, paracetamol or tramadol.
• Patients with a history of inadequate pain response (pain reduced was equal or less than 30%) to:
• pregabalin at maximum allowed treatment daily dose 600 mg, 3.2. duloxetine at maximum allowed treatment daily dose 120 mg, 3.3. venlafaxine at maximum allowed treatment daily dose 375 mg, 3.4. gabapentin on daily treatment dose more than 1800 mg 3.5. amitriptilin at maximum allowed treatment daily dose 150 mg.
• Patients, who are currently treated with a daily dose that exceeds:
• mg of pregabalin, 4.2. 60 mg of duloxetine, 4.3. 150 mg of venlafaxine, 4.4. 600 mg of gabapentin.
• Patients with an uncontrolled type 2 diabetes mellitus.
• The average scores of less than 20 on MoCA.
• Have any other type of neuropatic pain, contrasted to PDPN.
• Evidence of another cause of distal polyneuropathy other than diabetic.
• Have a serious (evaluated by physician) unstable cardiovascular (e.g. uncontrolled hypertension), hepatic, renal, respiratory, ophthalmologic, gastrointestinal, or hematologic illness, symptomatic peripheral vascular disease, malignant disease or other medical condition that could lead to hospitalisation during the course of the trial.
• Have a diagnosis or history of uncontrolled glaucoma.
• Known or suspected alcohol or drug abuse or addiction (excluding nicotine and caffeine).
• Patients with a history of depression (less than one year after completing the last medical treatment), mania, bipolar disorder, psychosis or schizophrenia.
• Pregnancy, lactation and women of child-bearing potential without highly effective\* or at least acceptable\*\* contraception (according to the Recommendations related to contraception and pregnancy testing in clinical trials).

Sponsors & Collaborators

• KRKA: lead
• 3ARH: collaborator
• INTERBORA: collaborator
• University Medical Centre Maribor: collaborator

Study Sites (13)

Opća bolnica Karlovac

Karlovac, Croatia

Location

Clinical Medical Center Osijek

Osijek, Croatia

Location

KB Merkur, Sveučilišna klinika Vuk Vrhovac

Zagreb, Croatia

Location

Klinička bolnica Sveti Duh

Zagreb, Croatia

Location

JZU Univerzitetska klinika za endokrinologija, dijabetes I metabolicki bolesti - Skopje

Skopje, North Macedonia

Location

JZU Univerzitetska klinika za nevrologija

Skopje, North Macedonia

Location

Gabinet Neurologiczny, prof. Adam Stępień

Warsaw, Poland

Location

Poradnia neurologiczna, Centrum terapii dzieci i Dorosłych FIMEDICA Sp. z o.o.

Warsaw, Poland

Location

Klinički centar Srbije

Belgrade, Serbia

Location

Klinički centar Niš

Niš, Serbia

Location

Klinički centar Vojvodine

Novi Sad, Serbia

Location

Zdravstveni dom Koper

Koper, 6000, Slovenia

Location

Clemenz Marjetka - Nevrološka Ordinacija

Ljubljana, 1000, Slovenia

Location

Related Publications (25)

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MeSH Terms

Interventions

Pregabalin; Duloxetine Hydrochloride

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Martin Rakuša

  University Medical Centre Maribor

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Treatment is started at Visit 2 with Pregabalin Krka or Dulsevia - according to randomisation.

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: January 29, 2020
• Study Start: November 12, 2019
• Primary Completion: December 21, 2021
• Study Completion: December 21, 2021
• Last Updated: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CR (4); SE (3); SL (2); PL (2); NO (2)