Dr. Harish. S 1, Dr. Beena Thomas 2 INTRODUCTION ABSTRACT

Transcription

1 International Journal of Research in Pharmacy and Biosciences Volume 3, Issue, January 6, PP ISSN (Print) & ISSN (Online) A Prospective, Randomized, Double Blind, Parallel Group, Placebo Controlled, Clinical Study to Evaluate the Efficacy and Safety of O liver-t in Patients with Hepatitis a Virus ABSTRACT Dr. Harish. S, Dr. Beena Thomas ICBio Clinical Research Pvt Ltd,# 6 &8 ICBio Tower, Yelahanka Main Road, Chikkabettahalli Vidyaranyapura, Bangalore, Karnataka, India SBL PVT. LTD., SBL House,, Commercial complex, Shrestha Vihar, Delhi, India Background: The medical term Hepatitis literally means inflammation of the liver. Chronic inflammation of the liver may result in liver damage or failure if left untreated. Hepatitis can be caused by many different things - drinking too much alcohol, traumatic injury, autoimmune disorders, an adverse drug reaction, or a virus such as the hepatitis A, B, C, D and E virus. Objectives: The aim of the study is to evaluate the safety and efficacy of Oliver-T in patients with Hepatitis A virus. Conclusion: Oliver-T is found effective in treating the Virus A hepatitis patients with positive outcome on the quality of life like Fever, Nausea, Vomiting, Loss of appetite, Vomiting, Painful Liver. Keywords: Alkaline phosphate (ALP), Oliver-T, Hepatitis INTRODUCTION Hepatitis A Hepatitis A (Infectious hepatitis, Epidemic hepatitis, Epidemic jaundice, Catarrhal jaundice, Type-A hepatitis, HA) is an acute infectious disease of the liver caused by the hepatitis A virus (HAV). Transmission of HAV is typically by the faecal-oral route. Infections occur early in life in areas where sanitation is poor and living conditions are crowded. What Causes the Disease? Hepatitis A is caused by infection with the hepatitis A virus (HAV), a non-enveloped, positive stranded RNA virus, classified within the genus hepatovirus of the picornavirus family. The virus interferes with the liver s functions while replicating in hepatocytes. The individual s immune system is then activated to produce a specific reaction to combat and possibly eradicate the infectious agent. As a consequence of pathological damage, the liver becomes inflamed. How is HAV Spread? As HAV is abundantly excreted in faeces, and can survive in the environment for prolonged periods of time, it is typically acquired by ingestion of faeces-contaminated food or water. Direct person-toperson spread is common under poor hygienic conditions. Occasionally, HAV is also acquired through sexual contact (anal-oral) and blood transfusions. When is Hepatitis a Contagious? In persons who develop clinically apparent hepatitis A, secretion of virus in stool at high titers begins one to three weeks prior to onset of illness, and may continue for several weeks at lower titers after jaundice occurs. Although the level of virus shedding does not correlate with the severity of liver disease, feces are highly infectious and therefore extremely contagious during all of this period. *Address for correspondence harish@icbiocro.com International Journal of Research in Pharmacy and Biosciences V3 I January 6 39

2 Pathogenesis of Hepatitis A Virus-induced cytopathology may not be responsible for the pathologic changes seen in HAV infection as liver disease may result primarily from immune mechanisms. Antigen-specific T- lymphocytes are responsible for the destruction of infected hepatocytes. Increased levels of interferon have been detected in the serum of HAV-infected patients and are presumably responsible for the reduction in virus burden seen in patients following the onset of clinical disease and in their symptoms. Rarely, patients with acute viral hepatitis A develop features of cholestasis. Side Effects and Safety Concerns To date, little is known about the safety of long-term use of supplements containing extracts of plants of the Phyllanthus genus. There's some concern that use of these supplements may increase the effects of certain medications (such as drugs used in the treatment of diabetes and high blood pressure). Therefore, it's important to consult a physician prior to taking supplements containing extracts of plants of the Phyllanthus genus in combination with other medications. OBJECTIVES Primary Objective To assess the efficacy of O Liver -T in the treatment of virus A hepatitis. Secondary Objective To evaluate the safety of O Liver -T in the treatment of virus A hepatitis. MATERIALS & METHODS Patients both male and female aged 8-4 years and those willing to give written informed consent were selected.they were with Hepatitis A Inclusion Criteria Patients with Virus A Hepatitis, female subjects who confirmed non pregnant status and agreed to comply with proper contraception throughout the study duration and patients willing and able to comply with all trial requirements were included in the study. The patients who are enrolled in the study were having the virus A hepatitis from several days. Exclusion Criteria Patients having the HbsAg in the serum, HIV infection, AIDS, Hepatitis C or other immune suppressive disorders, drug abuse within past years, Pregnancy and Breast feeding women were excluded from the study. Study was conducted by randomized, Double Blind, parallel group, placebo controlled clinical study by ICBio Clinical Research Pvt. Ltd. It involved in the clinical attendance of the subjects on recruitment and on follow up. Subjects enrolled in the study received Study drug (from Baseline visit to 84 days daily one teaspoonful three times a day, 3 minutes after Meals. Study drug would be the alternative or in addition to the therapies already being used. The safety and efficacy parameters were compared with baseline and follow-up data with laboratory investigations, demographics were analyzed in the study. Adverse events / side effects were noted for each follow-up visits Ethics Committee Approval All study related documents Protocol, Case Report Form, Dairy card, Investigator Brochure and Informed Consent Documents (English and Kannada Versions). Written Informed Consent was obtained from the subjects before the start of the trial and after due approval from IEC/IRB. Ethics Committee notifications as per the GCP guidelines issued by Central Drugs Standard Control Organization and Ethical guidelines for biomedical research on human subjects issued by Indian council of Medical Research has been followed during the Conduct of the Study (Clinical IEC- Independent Ethics Committee e for Ethics in Research and Approved on 6 th May ) Study Outcomes Primary Outcomes Relief from Clinical symptoms and changes of lab parameters Efficacy of drug International Journal of Research in Pharmacy and Biosciences V3 I January 6 4

3 Change Secondary Outcomes Incidence and rate of adverse events Safety Concern of the Drug Disposition of Subjects Total of subjects Drug A: Oliver-T (5 Subjects) Drug B: Placebo (5 Subjects) Visit Details The patients were screened and enrolled. The enrollment day was considered as the baseline Day and the patient were asked to visit on Day 3, Day 7, Day4, Day 8, Day 56, and Day 84 Statistical Analysis Data Analysis was carried out using 5% significance level and 8 % power for study using SAS. The difference within the group will be assessed using paired t-test. RESULTS In the study patients were screened and enrolled after meeting the inclusion Criteria and they are Randomised randomly into Drug A and Drug B. The enrolled subjects consisted of male and female Efficacy Analyses for Drug A Total Bilirubin of Total Bilirubin on Screening (Day ), Day 8, and Day 84 was found to be.84,.9694,.78 mg/dl. however statistical increase of 56.3%,68.6% in Total Bilirubin was found on Day 8 and Day 84 when Compared from Screening Total Bilirubin. Screening(mg/dl) Day 8(mg/dl) Change(mg/dl) Percentage change Total Bilirubin % Screening( mg/dl ) Day 84( mg/dl ) hange(mg/dl) Percentage Change Total Bilirubin % Total Bilirubin Screening Total Bilirubin International Journal of Research in Pharmacy and Biosciences V3 I January 6 4

4 Percentage Change Change Percentage Change Total Bilirubin 8.% 6.% 4.%.% 56.% 68.6%.% Direct Bilirubin of Direct Bilirubin on Screening (Day ), Day 8, and Day 84 was found to be.776,.57,.4 mg/dl. however statistical increase of 7.47%, 85.96% in Direct Bilirubin was found on Day 8 and Day 84 when Compared from Screening Direct Bilirubin Screening(mg/dl) Day 8(mg/dl) Change(mg/dl) Percentage change Direct Bilirubin % Screening( mg/dl ) Day 84( mg/dl ) Change(mg/dl) Percentage Change Direct Bilirubin % Direct Bilirubin Screening Direct Bilirubin Direct Bilirubin.% 8.% 6.% 4.%.%.% 7.47% 85.96% of on Screening (Day ), Day 8, and Day 84was found to be 73.9, 68.6, 8.64IU/L. however statistical increase of 7.84% and 6.3% in was found on Day 8 and Day 84 when Compared from Screening. International Journal of Research in Pharmacy and Biosciences V3 I January 6 4

5 Percentage Change Meam MEAN Change Screening(IU/L) Day 8(IU/L) Change(IU/L) Percentage change % Screening(IU/L) Day 84(IU/L) Change(IU/L) Percentage change % Screening of on Screening (Day ), Day 8, and Day 84 was found to be.34, 7.54, 5.78IU/L. however statistical increase of.93% and % in was found on Day 8 and Day 84 when Compared from Screening. Screening(IU/L) Day 8(IU/L) Change(IU/L) Percentage Increased % Screening(IU/L) Day 84(IU/L) Change(IU/L) Percentage Increased % Screening International Journal of Research in Pharmacy and Biosciences V3 I January 6 43

6 Change Percentage Change mean Change % 8.% 6.% 4.%.%.% 78.57%.93% Alkaline Phosphatase of ALP on Screening (Day ), Day 8, and Day 84 was found to be , 38.6, IU/L. however statistical increase of % and 68.5% in ALP was found on Day 8 and Day 84 when Compared from Screening ALP. Screening(IU/L) Day 8(IU/L) Change(IU/L) Percentage Increased ALP % Screening(IU/L) Day 84(IU/L) Change(IU/L) Percentage Increased ALP % Alkaline Phosphotase Screening Alkaline Phosphotase International Journal of Research in Pharmacy and Biosciences V3 I January 6 44

7 Percentage Change Change Percentage Change mean 8% 6% 4% Alkaline Phosphotase 68.5% % % 5% of on Screening (Day ), Day 8, and Day 84 was found to be 3.44, 4.34, 4.36 gms/l. However statistical increase of 6.36%, 7.7 % in was found on Day 8 and Day 84 when Compared from Screening Screening(gms/l) Day 8(gms/l) Change(gms/l) Percentage Change % Screening(gms/l) Day 84(gms/l) Change(gms/l) Percentage change % Screening % 7.7% 7.% 6.% 5.% 6.36% International Journal of Research in Pharmacy and Biosciences V3 I January 6 45

8 Percentage Change Change of on Screening (Day ), Day 8, and Day 84 was found to be.66, 3.4, 3.74gms/l. However statistical increase of 38.65%, 4.7% in was found on Day 8 and Day 84 when Compared from Screening Screening(gms/l) Day 8(gms/l) Change(gms/l) Percentage Change % Screening(gms/l) Day 84(gms/l) Change(gms/l) Percentage change % Screening(mg/dl) Day 8( mg/dl ) Change(mg/dl ) Percentage Change Direct Bilirubin % Screening % 4.% 39.% 38.% 37.% 4.7% 38.5% Efficacy Analysis for Drug B Total Bilirubin of Total Bilirubin on Screening (Day ), Day 8, and Day 84 was found to be.4758,.39,.7 mg/dl. However statistical increase of %, 55.7% in Total Bilirubin was found on Day 8 and Day 84 when compared from Screening Total Bilirubin Screening(IU/L) Day 8( IU/L ) Change( IU/L ) Percentage Change Total Bilirubin % Screening( IU/L ) Day 84( IU/L ) Change( IU/L ) Percentage change Total Bilirubin % International Journal of Research in Pharmacy and Biosciences V3 I January 6 46

9 Percentage Change Change Percentage Change Total Bilirubin Screening 6.% 5.% 4.% 3.%.%.%.% Total Bilirubin 55.7% 9.56% Direct Bilirubin of Direct Bilirubin on Screening (Day ), Day 8, and Day 84 was found to be.8658,.636,.574mg/dl. However statistical increase of.65%, 69.% in Direct Bilirubin was found on Day 8 and Day 84 when compared from Screening Direct Bilirubin Screening( mg/dl ) Day 84( mg/dl ) Change(mg/dl ) Percentage change Direct Bilirubin %.5 Direct Bilirubin % 6.% 4.%.%.% Direct Bilirubin 69.%.6% International Journal of Research in Pharmacy and Biosciences V3 I January 6 47

10 Percentage Change of on Screening (Day ), Day 8, and Day 84 was found to be 7.844, 7.84, IU/L. However statistical increase of.5%, 3.88 % in was found on Day 8 and Day 84 when compared from Screening Screening( IU/L ) Day 8( IU/L ) Change( IU/L ) Percentage change % Screening(IU/L) Day 84( IU/L ) Change( IU/L ) Percentage Change % Screening 3.% 5.%.% 5.%.% 5.%.%.% 3.88% 5 5 of on Screening (Day ), Day 8, and Day 84 was found to be 7.944, 5.574, IU/L. However statistical increase of.9%, % in was found on Day 8 and Day 84 when compared from Screening Screening( IU/L ) Day 8( IU/L ) Change( IU/L ) Percentage change % Screening(IU/L) Day 84( IU/L ) Change( IU/L ) Percentage Change % International Journal of Research in Pharmacy and Biosciences V3 I January 6 48

11 Percentage Change Change Screening % 35.% 3.% 5.%.% 5.%.% 5.%.% 35.58%.% Alkaline Phosphate of ALP on Screening (Day ), Day 8, and Day 84 was found to be , 45.58, 7.84 IU/L. However statistical increase of.435%, 7.5% in ALP was found on Day 8 and Day 84 when compared from Screening AL Alkaline Phosphate Screening International Journal of Research in Pharmacy and Biosciences V3 I January 6 49

12 Percentage Change Change Screening( IU/L ) Day 8( IU/L ) Change( IU/L ) Percentage change ALP % Screening(IU/L) Day 84( IU/L ) Change( IU/L ) Percentage Change ALP % Alkaline Phosphate 3.% 5.%.% 5.%.% 5.%.% Alkaline Phosphate 7.5%.43% of on Screening (Day ), Day 8, and Day 84 was found to be 3.478, 4.458, 3.684gms/l. However statistical increase of 8.7%, 5.9% in was found on Day 8 and Day 84 when compared from Screening Screening( gms/l ) Day 8( gms/l ) Change(gms/l ) Percentage change Screening(gms/l) Day 84( gms/l ) Change(gms/l ) Percentage Change % Screening International Journal of Research in Pharmacy and Biosciences V3 I January 6 5

13 Change Percentage Change mean Change Axis Title 3.% 5.%.% 5.%.% 5.%.% 8.7% 5.9% of on Screening (Day ), Day 8, and Day 84 was found to be.84,.86,.364gms/l. However statistical increase of 4.747%, 6.59% in was found on Day 8 and Day 84 when compared from Screening Screening(gms/l ) Day 8(gms/l ) Change(gms/l ) Percentage change % Screening(gms/l) Day 84( gms/l ) Change( gms/l) Percentage Change % Screening International Journal of Research in Pharmacy and Biosciences V3 I January 6 5

14 Percentage Change 7.% 6.59% 6.% 5.% 4.% 3.%.%.%.% 4.75% DISCUSSION & CONCLUSION The total number of subjects analyzed in the study is, of which 5 subjects were randomly assigned to the Drug A group and 5 subjects were randomly assigned to the Drug B group. The subjects were called for screening visit and were given the Informed consent and screening procedures were started. Once the subjects were screen passed, eventually the subjects were randomized in to the group A (drug), group B (placebo). The blind was broken after Day when as per the protocol the trial ended. All individuals, who were included in this study, were analyzed in this report. The data obtained from the two groups was analyzed statistically using paired t test as well as unpaired t test. The data was compared between the Active Groups (Group A) and Placebo Group (Group B) for the parameters including changes in clinical symptom assessment. The results obtained from Drug A is showing statistically significant difference from day 8in maximum subjects to Day 84 in all the subjects. From the Data obtained it was found that investigational product O Liver-T was shoeing significant percentage of increase in reduction of Symptoms of Viral Hepatitis A with no adverse events.furthermore, O Liver-T also significantly effective in the treatment of Viral Hepatitis A. REFERENCES [] Maton, Antheil; Jean Hopkins; Charles William McLaughlin; Susan Johnson; Maryann Quon Warner; David LaHart; Jill D. Wright (993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall.ISBN [] Zakim, David; Boyer, Thomas D. (). Hepatology: A Textbook of Liver Disease (in English) (4th Ed.).ISBN [3] Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (5).Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, MO: Elsevier Saunders. p ISBN [4] Ryder S, Beckingham I (). "Acute hepatitis".bmj 3 (779): [5] World Health Organization. "Hepatitis". World Health Organization. Retrieved 5 November 3. [6] Longo, DL, ed. (). "Chapter 36. Chronic Hepatitis" (Onlline). Harrison's Principles of Internal Medicine. (8th ed.). New York: McGraw-Hill. [7] Ryan KJ, Ray CG (editors) (4). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp ISBN [8] Matheny, SC; Kingery, JE ( December ). "Hepatitis A.". Am Fam Physician86 (): 7 34; quiz. PMID International Journal of Research in Pharmacy and Biosciences V3 I January 6 5

15 [9] "Hepatitis A Fact sheet N 38". World Health Organization. July 3. Retrieved February 4. [] Barker LF, Shulman NR, Murray R, Hirschman RJ, Ratner F, Diefenbach WC, Geller HM (996). "Transmission of serum hepatitis. 97". Journal of the American Medical Association 76 (): [] Mohd Hanafiah, K; Groeger, J; Flaxman, AD; Wiersma, ST (April 3). "Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology (Baltimore, Md.) 57 (4): [] Beckingham, IJ; Ryder, SD (). "Investigation of liver and biliary disease". BMJ (Clinical research ed.) 3 (777): [3] Goljan, Edward F. (7) Rapid Review Pathology, nd ed., Elsevier Health Sciences, pp , International Journal of Research in Pharmacy and Biosciences V3 I January 6 53