The purpose of the trial is to assess the efficacy of Pragiola® (pregabalin) and Dulsevia® (duloxetin) in patients with PDPN, investigate the effect of Pragiola® and Dulsevia® on pain and on quality of life (QOL), depression symptoms, cognitive functions, sleep quality and daytime sleepiness and assess the safety of Pragiola® and Dulsevia® in patients with PDPN.
Conditions
Interventions
Trade Name: Pragiola, 25 mg kapsulki, twarde
Pharmaceutical Form: Capsule, hard
Trade Name: Pragiola, 75 mg, kapsulki, twarde
Pharmaceutical Form: Capsule, hard
Trade Name: Pragiola, 150 mg, kapsulk
Sponsors
KRKA, d.d., Novo mesto
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female and male patients aged 18-85 years. 2. Patients with a history of type 2 diabetes mellitus according to The American Diabetes Association (ADA). 3. Patients with a diagnosis of painful diabetic peripheral neuropathy (PDPN) caused by type 2 diabetes mellitus based on Douleur Neuropathique questionnaire (DN4 =4). 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'). 5. Ability to adhere to trial protocol. 6. Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Patients who took PDPN medication and/or analgesics on a day of baseline visit. 2. 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. 3. Patients with a history of inadequate pain response (pain reduced was equal or less than 30%) to: 3.1 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. 4. Patients, who are currently treated with a daily dose that exceeds: 4.1 150 mg of pregabalin or 4.2 60 mg of duloxetine or 4.3 150 mg of venlafaxine or 4.4 600 mg of gabapentin. 5. Patients with an uncontrolled type 2 diabetes mellitus 6. The scores of less than 20 on Montreal cognitive assessment (MoCA). 7. Have any other type of neuropatic pain, contrasted to PDPN. 8. Evidence of another cause of distal polyneuropathy other than diabetic. 9. 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. 10. Have a diagnosis or history of uncontrolled glaucoma. 11. Known or suspected alcohol or drug abuse or addiction (excluding nicotine and caffeine). 12. Patients with any prior history of depression (less than one year after completing the last medical treatment), mania, bipolardisorder, psychosis or schizophrenia. 13. 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). 14. Patients with a history of epilepsy, stroke or neurodegenerative disease. 15. Patients taking Monoamine oxidase (MAO) inhibitors or are within one year of their withdrawal. 16. Acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C). 17. Patients with suspected Restless leg syndrome (RLS). 18. Abnormal thyroid-stimulating hormone (TSH) concentrations (according to the references value of the local laboratory). 19. Vitamin B12 and folic acid deficiency (according to the reference values of the local laboratory). 20. Surgical procedures planned to occur during trial (patients may be rescreened following completion of and recovery from the surgical procedure). 21. Concomitant treatment that might influence the final therapeutic effect of the tested active substances including non-medical treatments. 22. Patients who under the opinion of the investigator will not be compliant to the treatment or not be able to finish the trial for any other reason. *Highly effective contraception is: •combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation(oral, intravaginal, transdermal) •progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) •intrauterine device (IUD) •intrauterine hormone-releasing system (IUS) •bilateral tubal occlusion •vasectomised partner •sexual abstinence **Acceptable contraceptio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment;Main Objective: The purpose of the trial is to assess the efficacy of Pragiola® (pregabalin) and Dulsevia® (duloxetin) in patients with PDPN, investigate the effect of Pragiola® and Dulsevia® on pain and on quality of life (QOL), depression symptoms, cognitive functions, sleep quality and daytime sleepiness and assess the safety of Pragiola® and Dulsevia® in patients with PDPN.;Primary end point(s): 1. The proportion of patients with clinically meaningful improvement of pain in PDPN after a 12 week treatment with pregabalin. 2. The proportion of patients with clinically meaningful improvement of pain in PDPN after a 12 week treatment with duloxetine. Improvement of pain in PDPN is considered as clinically meaningful if reduction of average pain intensity in PDPN in last 24-h (measured by VAS) is equal or more than 30 % in comparison to the initial level (baseline) AND/OR if averege pain intensity in PDPN in last 24-h (measured by VAS) does not exceed 30 mm at the end of the trial (after 12 weeks). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The proportion of patients with reduction of pain in PDPN (measured by VAS) for equal or more than 30 % in comparison to the initial level (baseline) AND/OR with pain intensity in PDPN not exceeding 30 mm (measured by VAS) taking into consideration: i. current pain intensity (measured at doctor’s office) ii. average pain intensity in last 24-h iii. worst pain intensity in last 24-h [Time Frame: week 1, week 2, week 6, week 8]. 2. The proportion of patients with reduction of pain in PDPN for equal or more than 30 % (measured by VAS) in comparison to the initial level (baseline) AND/OR with pain intensity in PDPN not exceeding 30 mm (measured by VAS) taking into consideration: i. average pain intensity in last 4 weeks ii. worst pain intensity in last 4 weeks [Time Frame: week 8, week 12]. 3. Pain intensity difference in PDPN (measured by VAS) between each control visit/ phone call and the baseline value at Visit 2:i. current pain intensity ii. average pain intensity in last 24-h iii. worst pain intensity in last 24-h [Time Frame: week 1, week 2, week 6, week 8, week 12]. 4. Pain intensity difference in PDPN (measured by VAS) between Visits 4 and 5 and the baseline value at Visit 2: i. average pain intensity in last 4 weeks ii. worst pain intensity in last 4 weeks [Time Frame: week 8, week 12]. 5. The proportion of patients with reduction of pain in PDPN (measured by VAS) for equal or more than 50 % taking into consideration: i. current pain intensity (measured at doctor’s office) ii. average pain intensity in last 24-h iii. worst pain intensity in last 24-h [Time Frame: Baseline vs.: week 1, week 2, week 6, week 8, week 12]. 6. The proportion of patients with reduction of pain in PDPN (measured by VAS) for equal or more than 50 % taking into consideration: i. average pain intensity in last 4 weeks ii. worst pain intensity in last 4 weeks [Time Frame: week 8, week 12]. 7. The proportion of patients with eliminated pain in PDPN, which includes | — |
Countries
Croatia, North Macedonia, Poland, Serbia, Slovenia
Contacts
Public ContactClinical Trials Information
KRKA-POLSKA SP. Z O.O.
Outcome results
None listed