Ignite Creation Date:
2024-05-06 @ 2:13 PM
Last Modification Date:
2024-10-26 @ 1:27 PM
Study NCT ID:
NCT04246619
Status:
TERMINATED
Last Update Posted:
2022-04-07
First Post:
2020-01-24
Brief Title:
Efficacy of Pregabalin and Duloxetine in Patients With PDPN the Effect of Pain on Cognitive Function Sleep and Quality of Life
Sponsor:
KRKA
Organization:
KRKA
Study Overview
Official Title:
Efficacy of Pregabalin and Duloxetine in Patients With Painful Diabetic Peripheral Neuropathy PDPN the Effect of Pain on Cognitive Function Sleep and Quality of Life BLOSSOM
Status:
TERMINATED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The statistical analysis will still provide relevant results with the same statistical power as initially plannedCOVID-19 pandemic prolonged the recruiting period and consequently affected the costs of the clinical trial
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BLOSSOM
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 medicalsurgical history and concomitant diseases previous andor 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 heshe 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
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 medicalsurgical history and concomitant diseases previous andor 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 heshe 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
Detailed Description:
During the 3 months 12 weeks 5 visits and 2 phone calls are planned
Procedures and administration
On arrival at the trial site at Visit 1 the patient receives the complete information on the trial procedures The patient confirms his decision to participate by signing the informed consent form ICF 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 medicalsurgical history and concomitant diseases previous andor existing therapy of pain in PDPN concomitant medications with measurements and evaluation of pain according to VAS
Patient is instructed not to take any PDPN medication andor analgesics if existing on a day of Visit 2
Information obtained at Visit 1 is input in the eCRF
Visit 2 initial baseline visit 0-7 days after Visit 1
Investigator checks the results of laboratory tests of pregnancy test measures vital signs heart rate blood pressure evaluates pain in PDPN according to VAS separate assessments of current pain intensity average pain intensity in last 24-h worst pain intensity in last 24-h average pain intensity in last 4 weeks and worst pain intensity in last 4 weeks checks previous analgesic therapy and concomitant medications
If patient meets all inclusion and exclusion criteria heshe is eligible and will be randomly assigned automatically through electronic version of case report form eCRF into two therapy groups treatment arms
Investigator performs assessments of QoL with questionnaire SF-36 sleep quality and daytime sleepiness with questionnaires ISI and ESS depression with questionnaire MDI and adverse events
Administration
Eligible screened patients are randomly assigned into two therapy groups treatment arms
ARM 1 treatment with pregabalin Pregabalin Krka or ARM 2 treatment with duloxetine Dulsevia
Each patient receives a Patient diary number 1 including the doses of Pregabalin Krka or Dulsevia depending on randomization from Visit 2 day 1 till Phone call 1 scales for assessing the pain and with the date of Phone call 1
Treatment during PERIOD 1 FLEXIBLE-DOSE REGIMEN during the first 14 days 3 days in order to allow the investigator to give each patient an optimal dose of IMP
ARM 1 pregabalin Pregabalin Krka 25-150 mg day FLEXIBLE-DOSE REGIMEN Investigator can choose total Pregabalin Krka daily dose 25 mgday 50 mgday 75 mgday 150 mgday or 300 mgday from Phone call 1 further on
ARM 2 duloxetine Dulsevia 30-60 mg day FLEXIBLE-DOSE REGIMEN
Investigator can choose total Dulsevia daily dose 30 mgday or 60 mgday
At the Visit 2 RM is given to each patient to cover the treatment till the next Visit 3
Phone call 1 week 1 3 days At week 1 7 3 days after Visit 2 investigator calls the patient by phone and ask him or her about possible adverse events and to evaluate the pain intensity in PDPN by VAS which is a part of Patient diary 1
Investigator can adjust the dose of IMP during phone call
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS is NOT achieved the investigator can increase the dose
if bothersome adverse event occurs the investigator can decrease the dose if possible
The investigator also ask the patient if he or she is taking the IMP appropriately according to investigators instructions
NOTE On the next visit Visit 3 14 3 days after Visit 2 following daily doses should be achieved by each patient
ARM 1 Total Pregabalin Krka daily dose MINIMUM dose 150 mgday
ARM 2 Total Dulsevia daily dose MINIMUM dose 60 mgday
Visit 3 week 2 14 3 days after Visit 2 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
Investigator collects the Patient Diary 1 Data in Patient Diary 1 are checkedTreatment during PERIOD 2 it lasts 6 weeks
Treatment options
ARM 1 pregabalin Pregabalin Krka Investigator can choose total Pregabalin Krka daily dose 150 mgday or 300 mgday or 600 mgday
NOTE
If in the opinion of the investigator the minimum IMP dose of 150 mg of Pregabalin Krka 60 mg of Dulsevia can not be reached after Visit 3 the patient must be excluded from the trial
ARM 2 duloxetine Dulsevia
Investigator can choose
total Dulsevia daily dose 60 mgday or 90 mgday or total Dulsevia daily dose 120 mgday
once daily dosing by using available dosages the daily dose will be achieved with two devided doses of Dulsevia by using available dosages
ARM 1 pregabalin Pregabalin Krka
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is achieved during period 1 further treatment with Pregabalin Krka 150 mgday or 300 mgday in the period 2 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is NOT achieved further treatment with a dose of
150 mgday if patient was till now treated with equal dose or 300 mgday if patient was till now treated with equal dose to 150 mg or 300 mg or 600 mgday if patient was till now treated with equal dose to 300 mg is required
ARM 2 duloxetine Dulsevia
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is achieved further treatment with Dulsevia 60 mgday in the period 2 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is NOT achieved further treatment with the dose of
Dulsevia 60 mgday if patient was till now treated with equal dose or Dulsevia 90 mgday if patient was till now treated with lower dose or Dulsevia 120 mgday if patient was till now treted with lower dose is required
At the Visit 3 RM is given to each patient to cover the treatment till the next Visit 4 Patient is requested to bring packages with all blisters empty blisters and blister with unused IMPs and RM on the Visit 4
Each patient receives a Patient diary number 2 including the doses of Pregabalin Krka or Dulsevia depending on randomization from Visit 3 till Phone call 2 scales for assessing the pain and with the date of Phone call 2 28 3 days after Visit 3
Patient is requested to bring the Patient diary on the next visit
Information obtained at Visit 3 is input in the eCRF
Phone call 2 4 weeks28 3 days after visit 3 At week 6 28 3 days after Visit 3 the investigator again calls the patient by phone and asks him or her about possible bothersome adverse events and to evaluate the pain intensity in PDPN by VAS separate assessments of current pain intensity average pain intensity in last 24-h and worst pain intensity in last 24-h which is a part of Patient diary 2
The investigator can adjust the dose of Pregabalin Krka or Dulsevia if necessary If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS is NOT achieved the investigator can increase the dose and if bothersome adverse event occurs the investigator can decrease the dose to the previous dose
The investigator also checks if the patient takes the medicines appropriately according to investigators instructions
Visit 4 week 8 42 3 days after Visit 3 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 separate assessments of current pain intensity average pain intensity in last 24-h and worst pain intensity in last 24-h average pain intensity in last 4 weeks and worst pain intensity in last 4 weeks IMP are adjusted and assessment of adverse events is carried out Investigator collects the Patient Diary 2 Data in Patient Diary 2 are checked
Treatment options during PERIOD 3 it lasts 4 weeks ARM 1 pregabalin Pregabalin Krka
Investigator can choose
Total Pregabalin Krka daily dose 75 mgday 150 mgday 300 mgday or 600 mgday
only in case of bothersome adverse events
ARM 2 duloxetine Dulsevia Investigator can chooseTotal Dulsevia daily dose 30 mgday 60 mgday 90 mgday or 120 mgday only in case of bothersome adverse events
Arm 1 pregabalin Pregabalin Krka
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is achieved further treatment with previous dose in the period 3 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is NOT achieved on daily dose 150 mg further treatment with a dose of 150 mgday if patient was till now treated with equal dose or 300 mgday if patient was till now treated with lower or equal dose or 600 mgday if patient was till now treted with lower or equal dose is required
Arm 2 duloxetine Dulsevia
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is achieved further treatment with previous dose in the period 3 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is NOT achieved further treatment with a dose of
Dulsevia 60 mgday if patient was till now treated with equal dose or Dulsevia 90 mgday if patient was till now treated with lower or equal dose or Dulsevia 120 mgday if patient was till now treated with lower or equal dose
At the Visit 4 RM is given to each patient to cover the treatment till the next Visit 5
Visit 5 week 12 28 3 days after Visit 4 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
Compliance monitoring measurement of vital signs and concomitant medications are also carryed out by investigator
Procedures and administration
On arrival at the trial site at Visit 1 the patient receives the complete information on the trial procedures The patient confirms his decision to participate by signing the informed consent form ICF 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 medicalsurgical history and concomitant diseases previous andor existing therapy of pain in PDPN concomitant medications with measurements and evaluation of pain according to VAS
Patient is instructed not to take any PDPN medication andor analgesics if existing on a day of Visit 2
Information obtained at Visit 1 is input in the eCRF
Visit 2 initial baseline visit 0-7 days after Visit 1
Investigator checks the results of laboratory tests of pregnancy test measures vital signs heart rate blood pressure evaluates pain in PDPN according to VAS separate assessments of current pain intensity average pain intensity in last 24-h worst pain intensity in last 24-h average pain intensity in last 4 weeks and worst pain intensity in last 4 weeks checks previous analgesic therapy and concomitant medications
If patient meets all inclusion and exclusion criteria heshe is eligible and will be randomly assigned automatically through electronic version of case report form eCRF into two therapy groups treatment arms
Investigator performs assessments of QoL with questionnaire SF-36 sleep quality and daytime sleepiness with questionnaires ISI and ESS depression with questionnaire MDI and adverse events
Administration
Eligible screened patients are randomly assigned into two therapy groups treatment arms
ARM 1 treatment with pregabalin Pregabalin Krka or ARM 2 treatment with duloxetine Dulsevia
Each patient receives a Patient diary number 1 including the doses of Pregabalin Krka or Dulsevia depending on randomization from Visit 2 day 1 till Phone call 1 scales for assessing the pain and with the date of Phone call 1
Treatment during PERIOD 1 FLEXIBLE-DOSE REGIMEN during the first 14 days 3 days in order to allow the investigator to give each patient an optimal dose of IMP
ARM 1 pregabalin Pregabalin Krka 25-150 mg day FLEXIBLE-DOSE REGIMEN Investigator can choose total Pregabalin Krka daily dose 25 mgday 50 mgday 75 mgday 150 mgday or 300 mgday from Phone call 1 further on
ARM 2 duloxetine Dulsevia 30-60 mg day FLEXIBLE-DOSE REGIMEN
Investigator can choose total Dulsevia daily dose 30 mgday or 60 mgday
At the Visit 2 RM is given to each patient to cover the treatment till the next Visit 3
Phone call 1 week 1 3 days At week 1 7 3 days after Visit 2 investigator calls the patient by phone and ask him or her about possible adverse events and to evaluate the pain intensity in PDPN by VAS which is a part of Patient diary 1
Investigator can adjust the dose of IMP during phone call
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS is NOT achieved the investigator can increase the dose
if bothersome adverse event occurs the investigator can decrease the dose if possible
The investigator also ask the patient if he or she is taking the IMP appropriately according to investigators instructions
NOTE On the next visit Visit 3 14 3 days after Visit 2 following daily doses should be achieved by each patient
ARM 1 Total Pregabalin Krka daily dose MINIMUM dose 150 mgday
ARM 2 Total Dulsevia daily dose MINIMUM dose 60 mgday
Visit 3 week 2 14 3 days after Visit 2 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
Investigator collects the Patient Diary 1 Data in Patient Diary 1 are checkedTreatment during PERIOD 2 it lasts 6 weeks
Treatment options
ARM 1 pregabalin Pregabalin Krka Investigator can choose total Pregabalin Krka daily dose 150 mgday or 300 mgday or 600 mgday
NOTE
If in the opinion of the investigator the minimum IMP dose of 150 mg of Pregabalin Krka 60 mg of Dulsevia can not be reached after Visit 3 the patient must be excluded from the trial
ARM 2 duloxetine Dulsevia
Investigator can choose
total Dulsevia daily dose 60 mgday or 90 mgday or total Dulsevia daily dose 120 mgday
once daily dosing by using available dosages the daily dose will be achieved with two devided doses of Dulsevia by using available dosages
ARM 1 pregabalin Pregabalin Krka
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is achieved during period 1 further treatment with Pregabalin Krka 150 mgday or 300 mgday in the period 2 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is NOT achieved further treatment with a dose of
150 mgday if patient was till now treated with equal dose or 300 mgday if patient was till now treated with equal dose to 150 mg or 300 mg or 600 mgday if patient was till now treated with equal dose to 300 mg is required
ARM 2 duloxetine Dulsevia
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is achieved further treatment with Dulsevia 60 mgday in the period 2 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with baseline is NOT achieved further treatment with the dose of
Dulsevia 60 mgday if patient was till now treated with equal dose or Dulsevia 90 mgday if patient was till now treated with lower dose or Dulsevia 120 mgday if patient was till now treted with lower dose is required
At the Visit 3 RM is given to each patient to cover the treatment till the next Visit 4 Patient is requested to bring packages with all blisters empty blisters and blister with unused IMPs and RM on the Visit 4
Each patient receives a Patient diary number 2 including the doses of Pregabalin Krka or Dulsevia depending on randomization from Visit 3 till Phone call 2 scales for assessing the pain and with the date of Phone call 2 28 3 days after Visit 3
Patient is requested to bring the Patient diary on the next visit
Information obtained at Visit 3 is input in the eCRF
Phone call 2 4 weeks28 3 days after visit 3 At week 6 28 3 days after Visit 3 the investigator again calls the patient by phone and asks him or her about possible bothersome adverse events and to evaluate the pain intensity in PDPN by VAS separate assessments of current pain intensity average pain intensity in last 24-h and worst pain intensity in last 24-h which is a part of Patient diary 2
The investigator can adjust the dose of Pregabalin Krka or Dulsevia if necessary If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS is NOT achieved the investigator can increase the dose and if bothersome adverse event occurs the investigator can decrease the dose to the previous dose
The investigator also checks if the patient takes the medicines appropriately according to investigators instructions
Visit 4 week 8 42 3 days after Visit 3 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 separate assessments of current pain intensity average pain intensity in last 24-h and worst pain intensity in last 24-h average pain intensity in last 4 weeks and worst pain intensity in last 4 weeks IMP are adjusted and assessment of adverse events is carried out Investigator collects the Patient Diary 2 Data in Patient Diary 2 are checked
Treatment options during PERIOD 3 it lasts 4 weeks ARM 1 pregabalin Pregabalin Krka
Investigator can choose
Total Pregabalin Krka daily dose 75 mgday 150 mgday 300 mgday or 600 mgday
only in case of bothersome adverse events
ARM 2 duloxetine Dulsevia Investigator can chooseTotal Dulsevia daily dose 30 mgday 60 mgday 90 mgday or 120 mgday only in case of bothersome adverse events
Arm 1 pregabalin Pregabalin Krka
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is achieved further treatment with previous dose in the period 3 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is NOT achieved on daily dose 150 mg further treatment with a dose of 150 mgday if patient was till now treated with equal dose or 300 mgday if patient was till now treated with lower or equal dose or 600 mgday if patient was till now treted with lower or equal dose is required
Arm 2 duloxetine Dulsevia
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is achieved further treatment with previous dose in the period 3 is required
If average pain intensity in PDPN in last 24-h equal or below 30 mm measured by VAS or reduction of pain equal or more than 30 compared with Visit 3 is NOT achieved further treatment with a dose of
Dulsevia 60 mgday if patient was till now treated with equal dose or Dulsevia 90 mgday if patient was till now treated with lower or equal dose or Dulsevia 120 mgday if patient was till now treated with lower or equal dose
At the Visit 4 RM is given to each patient to cover the treatment till the next Visit 5
Visit 5 week 12 28 3 days after Visit 4 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
Compliance monitoring measurement of vital signs and concomitant medications are also carryed out by investigator
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-004341-24 | EUDRACT_NUMBER | None | None |