CTRI/2024/03/063691 [Registered on: 06/03/2024] Trial Registered Prospectively
Last Modified On:
05/11/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to assess the efficacy and safety of Pregabalin, Duloxetine and Mecobalamin Capsules in neuropathic pain patients.
Scientific Title of Study
A Multicentric, Randomized, Double Blind, Double Dummy, Active Controlled, Prospective, Parallel Group, Comparative, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Pregabalin, Duloxetine (As Gastro Resistant Pellets) and Mecobalamin Capsules Versus Fixed Dose Combination of Pregabalin, Nortriptyline and Mecobalamin Tablets for the Treatment of Patients with Diabetic Peripheral Neuropathic Pain with Coexistent Vitamin B12 Deficiency.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CT/2023/26, Version No.: 00 and Dated Apr 21, 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Aditya Kaushik
Designation
President - Drug Regulatory Affairs
Affiliation
Synokem Pharmaceuticals Ltd.
Address
Synokem Pharmaceuticals Ltd.,
14/486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi.
New Delhi DELHI 110087 India
Phone
9818637035
Fax
Email
aditya.kaushik@synokempharma.com
Details of Contact Person Scientific Query
Name
Dr Aditya Kaushik
Designation
President - Drug Regulatory Affairs
Affiliation
Synokem Pharmaceuticals Ltd.
Address
Synokem Pharmaceuticals Ltd.,
14/486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi.
DELHI 110087 India
Phone
9818637035
Fax
Email
aditya.kaushik@synokempharma.com
Details of Contact Person Public Query
Name
Dr Aditya Kaushik
Designation
President - Drug Regulatory Affairs
Affiliation
Synokem Pharmaceuticals Ltd.
Address
Synokem Pharmaceuticals Ltd.,
14/486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi.
Prakash Medical College Institutional Ethics Committee, Prakash Institute of Medical Sciences & Research (PIMS&R)
Submittted/Under Review
Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital, Kolhapur Institutional Ethics Committee 2 (RCSMGMCIEC2)
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: E114||Type 2 diabetes mellitus with neurological complications,
Intervention / Comparator Agent
Type
Name
Details
Intervention
FDC of Pregabalin 75 mg + Duloxetine 20 mg + Mecobalamin 1500 mcg Capsules and Matching Placebo Tablet of Reference Product
Patients will be advised to take one tablet once a day orally every night at bedtime for 12 weeks.
Matching Placebo of either drug will be given to patients of respective arm. Study drug should be taken along with matching placebo of test or reference product preferably at the same time.
Intervention
FDC of Pregabalin 75 mg + Duloxetine 30 mg + Mecobalamin 1500 mcg Capsules and Matching Placebo Tablet of Reference Product
Patients will be advised to take one tablet once a day orally every night at bedtime for 12 weeks.
Matching Placebo of either drug will be given to patients of respective arm. Study drug should be taken along with matching placebo of test or reference product preferably at the same time.
Comparator Agent
FDC of Pregabalin 75 mg + Nortriptyline 10 mg + Mecobalamin 1500 mcg Tablets and Matching Placebo Capsule of Test Product
Patients will be advised to take one tablet once a day orally every night at bedtime for 12 weeks.
Matching Placebo of either drug will be given to patients of respective arm. Study drug should be taken along with matching placebo of test or reference product preferably at the same time.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients aged between 18 and 65 years (both inclusive).
2. Patients with documented diagnosis of type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) levels less than or equal to 11% and having pain associated with diabetic peripheral neuropathy for more than or equal to 6 months.
3. Patients who experience pain associated with diabetic peripheral neuropathy and having visual analogue scale (VAS) score more than or equal to 30 at screening and baseline visit.
4. Patients with decreased vitamin B12 levels (less than 200 pg per mL) at screening visit.
5. Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study. WOCBP must have a negative urine pregnancy test at screening or baseline visit.
6. Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
7. Patients willing to comply with all the protocol requirements.
ExclusionCriteria
Details
1. Patients with history of hypersensitivity to either of the study medication or related class of drugs.
2. Patients with prior therapy with Pregabalin or Duloxetine or Nortriptyline and having any other neurologic disorders unrelated to diabetic peripheral neuropathic pain were excluded.
3. Patients who are experiencing non-diabetic peripheral neuropathy-related pain.
4. Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the UNL and or Total bilirubin more than 1.5X the UNL) at screening.
5. Patients with clinically significant impaired renal function (Serum creatinine more than 1.5X the ULN) at screening.
6. Patients having serum sodium level less than 130 mmol per L at screening.
7. Patients with history of type 1 diabetes mellitus.
8. Patients with uncontrolled hypertension with sitting systolic BP more than or equal to 160 mmHg and or diastolic BP more than or equal to 100 mmHg at screening.
9. Patients with any abnormality on 12-lead ECG at screening that in the opinion of the investigator is clinically significant and is judged as potential risk for patient’s participation in the study.
10. Patients with history of suicidal thoughts and behavior.
11. Patients with history of clinically significant medical illness in past 3 months, such as cardiovascular disease (e.g., MI, uncontrolled hypertension, orthostatic hypotension), falls and syncope, central nervous system diseases (e.g., seizure, bipolar disorder, depression, generalized anxiety disorder), liver disease, angioedema, peripheral edema, angle-closure glaucoma, urinary retention, bleeding disorder or any other disorder which may compromise safety of patient as per investigator discretion.
12. Patients treated with drugs that impair metabolism of serotonin (mono-amine oxidase inhibitors, Linezolide, Methylene Blue) or serotonergic agents other than study drugs (SSRIs, SNRIs, triptans, antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone, amphetamines) or corticosteroids within past 4 weeks prior to screening.
13. Patient treated with topical or systemic pain medications (e.g., NSAIDs, local anesthetics, Methyl Salicylate, Capsaicin, Tramadol, Tapentadol etc.) within past 2 weeks prior to baseline.
14. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
15. Female patients who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (like hormonal, barrier methods or intrauterine device).
16. Patients with a history of any malignancy.
17. Patients with history of infection with hepatitis B, hepatitis C or HIV.
18. Patients with a history of substance abuse or dependence that in the opinion of the Investigator is considered to interfere with the patient’s participation in the study.
19. Patients with any psychiatric or mental disease compromise the ability to give the consent for participation in the study.
20. Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
21. Patients currently taking any of the prohibited medications(s) and inability or unwillingness to discontinue them for the entire study period.
22. Patients with suspected inability or unwillingness to comply with the study procedures.
23. Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Mean change in visual analogue scale (VAS) score from baseline to end of the study visit (12 weeks).
Visit 1 - Screening visit,
Visit 2 - Baseline or Randomization (Day 1),
Visit 3 - Follow up visit or Week 2 (Day 14±2),
Visit 4 - Follow up visit or Week 4 (Day 28±2),
Visit 5 - Follow up visit or Week 8 (Day 56±2) and
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Secondary Outcome
Outcome
TimePoints
Mean change in Leeds assessment of neuropathic symptoms and signs (LANSS) pain scale score from baseline to end of the study visit (12 weeks).
Visit 1 - Screening visit,
Visit 2 - Baseline or Randomization (Day 1),
Visit 3 - Follow up visit or Week 2 (Day 14±2),
Visit 4 - Follow up visit or Week 4 (Day 28±2),
Visit 5 - Follow up visit or Week 8 (Day 56±2) and
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Mean change in the vitamin B12 levels from baseline to end of the study visit (12 weeks).
Visit 1 - Screening visit and
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Patient global impression of change at the end of the study visit (12 weeks).
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Investigator global impression of change at the end of the study visit (12 weeks).
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Consumption of rescue medication (number of Paracetamol Tablets consumed) during the study.
Visit 3 - Follow up visit or Week 2 (Day 14±2),
Visit 4 - Follow up visit or Week 4 (Day 28±2),
Visit 5 - Follow up visit or Week 8 (Day 56±2) and
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Target Sample Size
Total Sample Size="258" Sample Size from India="258" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
trial is amulticentric, randomized, double
blind, double dummy, active controlled, prospective, parallel group,
comparative, phase III clinical study to evaluate the efficacy, safety and
tolerability of fixed dose combination of Pregabalin, Duloxetine (as gastro
resistant pellets) and Mecobalamin Capsules versus fixed dose combination of
Pregabalin, Nortriptyline and Mecobalamin Tablets for the treatment of patients
with diabetic peripheral neuropathic pain with coexistent vitamin B12
deficiency.
Patients
who are willing and able to participate in the study will sign and date the
Informed Consent Form on the day of screening visit (Visit 1). During this
screening period, patients who are willing to give consent will be evaluated
for all the eligibility criteria. Eligible patients aged between 18 to 65 years
(both inclusive) fulfilling all inclusion criteria and none of the exclusion
criteria will be considered for the study.
After confirming the inclusion/exclusion criteria the
subject will be randomized and provided with study medication at randomization
visit. Subjects will be provided with a diary at randomization visit, which
need to be brought along with in each subsequent visit till the last visit.
Follow up visits will be done on week 2/day 14(±2), week 4/day 28(±2), week 8/day
56(±2) and week 12/day 84(±2) (Final Visit) of treatment to assess efficacy, safety
and tolerability.
Patients will be assigned to either of the three arms
i.e., Arm A or Arm B or Arm C consisting of FDC of Pregabalin 75 mg +
Duloxetine 20 mg + Mecobalamin 1500 mcg Capsules or FDC of Pregabalin 75 mg +
Duloxetine 30 mg + Mecobalamin 1500 mcg Capsules or FDC of Pregabalin 75 mg +
Nortriptyline 10 mg + Mecobalamin 1500 mcg Tablets. Patients will be advised to
take one tablet once a day orally every night at bedtime for 12 weeks. Matching
Placebo of either drug will be given to patients of respective arm. Study drug
should be taken along with matching placebo of test or reference product
preferably at the same time.