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.
试验速览
- 阶段
- 3 期
- 状态
- Not Applicable
- 入组人数
- 258
- 试验地点
- 8
- 主要终点
- Mean change in visual analogue scale (VAS) score from baseline to end of the study visit (12 weeks).
研究概览
简要总结
This trial is 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.
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients aged between 18 and 65 years (both inclusive).
- •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.
- •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.
- •Patients with decreased vitamin B12 levels (less than 200 pg per mL) at screening visit.
- •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.
- •Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
- •Patients willing to comply with all the protocol requirements.
排除标准
- •Patients with history of hypersensitivity to either of the study medication or related class of drugs.
- •Patients with prior therapy with Pregabalin or Duloxetine or Nortriptyline and having any other neurologic disorders unrelated to diabetic peripheral neuropathic pain were excluded.
- •Patients who are experiencing non-diabetic peripheral neuropathy-related pain.
- •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.
- •Patients with clinically significant impaired renal function (Serum creatinine more than 1.5X the ULN) at screening.
- •Patients having serum sodium level less than 130 mmol per L at screening.
- •Patients with history of type 1 diabetes mellitus.
- •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.
- •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.
- •Patients with history of suicidal thoughts and behavior.
- •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.
- •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.
- •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.
- •Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
- •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).
- •Patients with a history of any malignancy.
- •Patients with history of infection with hepatitis B, hepatitis C or HIV.
- •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.
- •Patients with any psychiatric or mental disease compromise the ability to give the consent for participation in the study.
- •Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
- •Patients currently taking any of the prohibited medications(s) and inability or unwillingness to discontinue them for the entire study period.
- •Patients with suspected inability or unwillingness to comply with the study procedures.
- •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.
结局指标
主要结局
Mean change in visual analogue scale (VAS) score from baseline to end of the study visit (12 weeks).
时间窗: 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).
次要结局
- 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,)
- Mean change in the vitamin B12 levels from baseline to end of the study visit (12 weeks).(Visit 1 - Screening visit and)
- 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),)
研究者
Dr Aditya Kaushik
Synokem Pharmaceuticals Ltd.