A Phase IIb/III, Multi-Center, Randomized, Parallel Group, Controlled Study to Evaluate the Efficacy and Safety of 750 mg and 1000 mg of LLL-3348 of Lupin Limited in Moderate to Severe Chronic Stable Plaque Type of Psoriasis
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 330
- 试验地点
- 12
- 主要终点
- Proportion of patients with > 75% reduction in PASI score from baseline to the end of treatment
研究概览
简要总结
This is a randomized, open lablel, parallel group, multi-centre study to compare the efficacy and safety of LLL-3348, in doses of 750 mg and 1000 mg administered once daily in comparison to methotrexate administered as per the Dermatologists judgment in the patient with moderate to severe chronic stable plaque type of psoriasis that will be conducted in 12 centers in India. The primary objectives are to determine the safety and tolerability of 750 mg of LLL-3348 once daily for 16 weeks as compared to Methotrexate and to determine the reduction in Psoriasis Area and Severity Index (PASI) score by >75% from baseline to the end of treatment. The secondary objectives are to compare the Physician's Global Assessment (PGA) score of LLL-3348 versus methotrexate after 1 month of treatment onwards till the end of treatment and to evaluate the rebound during the treatment or recurrence during treatment free follow-up period. In the initial phase IIb part of the study patients were randomized to LLL-3348 750 mg or 1000 mg or methotrexate. During this period, the objective was to find the safety profile of the different doses of LLL-3348. Following analysis of safety profile of the two doses at the end of phase IIb part of the study, the safe dose recommended is 750 mg for further Phase III study. The phase III part of the study is planned to establish further safety and efficacy. A new set of patients will now be randomized to LLL-3348 750 mg and methotrexate (Active comparator) in the phase III, randomized, parallel group, controlled study. In view of the large sample size and chronic nature of the disease a few more sites will be introduced. All the Assessors of the disease will be unaware of the trial medication given.
研究设计
- 分配方式
- Computer generated randomization
- 盲法
- Outcome Assessor Blinded
入排标准
入选标准
- •Patients with moderate to severe Chronic Stable Plaque Psoriasis with PASI score of ≥
- •Either males or females aged 18 to 60 years.
- •Patients who have not used for 2 weeks the anti-psoriatic therapy including ultraviolet D phototherapy, topical corticosteroids, vitamin A or D analogues or anthralin and who have not used for 4 weeks the anti-psoriatic therapy including PUVA, or any systemic anti-psoriatic treatment (systemic corticosteroids, immunosuppresants or any other systemic therapy including those on Methotrexate 2 months prior to screening).
- •Patients willing to sign Informed Consent Form.
排除标准
- •Patients who have been treated with Methotrexate within 2 months prior to screening.
- •Pregnant women or nursing mothers
- •Women of child bearing potential & all men who are not willing to use reliable & effective contraceptive measures during the course of the study & at least 3 months after the last visit.
- •Patients with guttate, erythrodermic, or pustular psoriasis and any other active skin conditions that would interfere with evaluations.
- •Patients with a co-existing disease for which they have to take a concomitant medication with anti-psoriasis activity, such as: systemic corticosteroids, immuno-suppressants etc.
- •Patient with active uncontrolled infectious disease.
- •Patients with any serious disease that would interfere with the compliance to study protocol and proper completion of the trial
- •Patient with severe anemia, leucopenia or thrombocytopenia or any other clinically significant blood disorders
- •Patients with hepatitis/ fibrosis, cirrhosis, or any other active hepatic disorders or any abnormal kidney functions
- •Patients with any screening laboratory values that deviate from upper or lower limits of the reference range, except for clinically insignificant deviations as determined by the Investigator
- •Serum SGOT and SGPT > 3 X , Alkaline Phosphatase > 1.5 X , Creatinine > 1.5 X and Total bilirubin >1.5 X the Upper Limit of Normal (ULN) of the reference range at the screening assessment
- •Patient receiving medicines with antifolate properties (e.g., co-trimoxazole)
- •Patients with major psychiatric disorder that is not well controlled with treatment
- •Patients with history of acute myocardial infarction or stroke within 6 months of signing informed consent
- •Patients with Alcohol or drug dependence
- •Patients who have received any other investigational drug within 4 weeks prior to screening.
- •Patients who are doubtful to comply with study procedures for social or psychological reason
- •Patients with clinically significant cardiovascular, haemopoetic, endocr.
结局指标
主要结局
Proportion of patients with > 75% reduction in PASI score from baseline to the end of treatment
时间窗: PASI will be assessed at screening visit, at randomization and every 4 weeks till teh end of the study treatment
次要结局
- 1.Proportion of patients with > 50% reduction in PASI Score from baseline to the end of treatment i.e. after 16 Weeks2.Proportion of patients with improvement in PGA score 3.Incidence of rebound and relapse(PASI at Screening, Randomization, and at every visit every 4 weeks till end of the treatmentPGA at randomization and every 4 weeks till end of the treatment)