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1 Clinical Trial Details (PDF Generation Date :- Tue, 09 Apr :19:44 GMT) CTRI Number CTRI/2010/091/ [Registered on: 17/02/2010] - Last Modified On 11/04/2013 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study No Interventional Drug Randomized, Parallel Group, Placebo Controlled Trial A clinical study to assess safety, tolerability and pharmacokinetics of curcumin and biocurcumax administered with and without a fixed dose of artesunate in healthy adult male volunteers. A double blind, randomized, placebo controlled Phase I trial to assess safety, tolerability and pharmacokinetics of curcumin and biocurcumax administered with and without a fixed dose of artesunate in healthy adult male volunteers. Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) Details Contact Person (Public Query) NCE_101_ARTCB_08 Protocol Number Details of Principal Investigator Monika Tandon, MD, DM Phone Fax Clinical Pharmacology Unit Ranbaxy Research Laboratories, Fortis Hospital Complex monika.tandon@ranbaxy.com Details Contact Person (Scientific Query) Dr. Neena Valecha NA National Institute of Malaria Research Sector 8, Phone Fax neenavalecha@gmail.com Details Contact Person (Public Query) Dr. Neena Valecha National Institute of Malaria Research Sector 8, Phone page 1 / 5

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Details of Ethics Committee Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Inclusion Criteria Fax neenavalecha@gmail.com Source of Monetary or Material Support > National Institute of Malaria Research Ministry of Health and Family Welfare 22-Sham Nath Marg, Delhi Type of Sponsor NA List of Countries of Principal Investigator Monika Tandon, MD, DM Primary Sponsor Details Department of Biotechnology Ministry of Science & Technology Block No:2, 7th Floor, CGO Complex Lodi Road, New Delhi? INDIA of Site Site Phone/Fax/ Clinical Pharmacology Unit Ranbaxy Research Laboratories,B-22, Sector 62, Fortis Hospital Complex monika.tandon@ranbax y.com of Committee Approval Status Date of Approval Is Independent Ethics Committee? Institutional Review Board, Fortis Hospital, B-22, Sector 62, Noida, UP Status Approved 08/01/2010 No Date Approved/Obtained 03/08/2009 Health Type Condition Antimalarial in healthy adult male human volunteers Type Details Intervention Artesunate 200 mg Intervention Biocurcumax (Curcumin dissolved in turmeric oil) 250 mg Intervention Curcumin 500 Mg Comparator Agent Age From Age To Gender Details Matched placebo formulations of each of the above mentioned Investigational Products Year(s) Year(s) Male Inclusion Criteria Subjects to be enrolled in this trial must fulfil all of these criteria:? Sex: male? Age: yr old, both inclusive page 2 / 5

3 ? Be neither overweight nor underweight for his height as per the Life Insurance Corporation of height/weight chart for non-medical cases? Vital Signs: 90? SBP?140 mmhg, DBP > 90 mmhg, 60?HR?90? Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; and to comply with the requirements of the entire study? Informed Consent: signed written informed consent prior to inclusion in the study Exclusion Criteria Details Exclusion Criteria Subjects meeting any of these criteria will not be enrolled in the study:? History of hypersensitivity and / or intolerance to artesunate, curcumin or biocurcumax or any other related compounds. Subjects meeting any of these criteria will not be enrolled in the study:? History of hypersensitivity and / or intolerance to artesunate, curcumin or biocurcumax or any other related compounds. Subjects meeting any of these criteria will not be enrolled in the study:? History of hypersensitivity and / or intolerance to artesunate, curcumin or biocurcumax or any other related compounds.? History of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study.? ECG (12 leads): clinically relevant abnormalities; QTc interval > 450 msec.? Clinically abnormal Chest X-ray.? Physical findings: clinically relevant abnormal physical findings (including body temperature) suggesting underlying pathologies or those which could interfere with the objectives of the study.? Gastrointestinal disorders likely to influence drug absorption including acute gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea, heart burn), preceding one week to admission.? Presence of values, which are clinically significantly different from normal reference ranges (as defined in Appendix II and III) for hemoglobin, hematocrit, total white blood cells count, differential WBC count or platelet count.? Presence of values which are significantly different from normal reference ranges ( as defined in Appendix III and IV) and/or judged clinically significant for blood urea nitrogen, serum creatinine, uric acid, sodium, potassium, alkaline phosphatase, aspartate amino transferase (AST), alanine amino transferase (ALT), total bilirubin, total protein, sodium, potassium or plasma glucose.? Clinically abnormal chemical and microscopic examination of urine defined as presence of RBC, WBC (>4/HPF), epithelial cells (>4/HPF), glucose (positive) or proteins (positive).? Presence of disease markers of HIV 1 or 2, Hepatitis B or C viruses or syphilis infection.? Positive for urinary screen testing of drugs of abuse (Opiates, cannabinoids, barbiturates, amphetamines, cocaine, benzodiazepines.).? Any evidence of organ dysfunction or any clinically significant deviation from the normal, in physical or clinical determinations.? Diseases: relevant history of renal, hepatic, cardiovascular, respiratory, skin, haematological, endocrine, neurological or gastrointestinal diseases. History of depression, psychosis, schizophrenia or any other severe psychiatric diseases, or epilepsy, or any other illness that may interfere with the aim of the study. History of any significant illness in the 4 weeks preceding the screening? Medications: history of any antimalarial treatment in the previous 3 months, other medications including over the counter medications (OTC) during the 4 weeks period prior to the onset of the study.? Investigational drug trials: participation in the evaluation of any drug including artesunate and curcumin and/or biocurcumax (curcumin dissolved in turmeric oil) in the 3 months prior to the start of the study? Blood donation: subjects who, through completion of this study, would have donated and/or lost more than page 3 / 5

4 Method of Generating Random Sequence Method of Concealment Blinding/Masking Computer generated randomization Pre-numbered or coded identical Containers Participant, Investigator and Outcome Assessor Blinded 350 ml of blood in the past 3 months? History of drug dependence or excessive alcohol intake on a habitual basis of more than 2 units of alcoholic beverages per day (1 unit equivalent to half pint of beer or 1 glass of wine or 1 measure of spirit) or have difficulty in abstaining for the duration of the study.? Regular smokers who smoke more than 10 cigarettes daily or have difficulty abstaining from smoking for the duration of study Primary Outcome Outcome Timepoints Safety and tolerability of curcumin and biocurcumax will be assessed after single and ascending multiple doses when administered alone or in combination with artesunate,.on the basis of AEs, vital signs (BP, pulse rate, and body temperature), ECG, and clinical laboratory results as per the study protocol Secondary Outcome Outcome Timepoints Target Sample Size Phase of Trial Phase 1 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Pharmacokinetics of single dose of curcumin and biocurcumax assessed on Day 1 in the absence of artesunate Pharmacokinetics of single dose of artesunate 200 mg assessed on Day 1 in the absence of curcumin and biocurcumax Assess drug-drug interaction by comparing pharmacokinetic profile of each drug on Day 1 with the corresponding one of Day 3. Assess effect of multiple dosing on pharmacokinetics of each drug by comparing profiles of Day 3 with corresponding ones of Day 5. Pharmacokinetics parameters: Cmax, Tmax, T1/2, AUC0-t, AUC0-, CL/F, Vd/Fs and accumulation of curcumin or biocurcumax (curcumin dissolved in turmeric oil) alone and with artesunate after multiple dose at three dose levels Total Sample Size=48 Sample Size from =48 17/02/2010 No Date Specified Years=0 Months=3 Days=0 Completed As per the study protocol Artemisinin and its derivatives (artesunate, artemether, artemotil, dihydroartemisinin) produce rapid clearance of parasitaemia and rapid resolution of symptoms. They reduce parasite numbers by a factor of approximately 10,000 in each asexual cycle, which is more than other current antimalarials (which reduce parasite numbers 100- to 1000-fold per cycle). Artemisinin and its derivatives are page 4 / 5

5 Powered by TCPDF ( eliminated rapidly. When given in combination with rapidly eliminated compounds (tetracyclines, clindamycin), a 7-day course of treatment with an artemisinin compound is required; but when given in combination with slowly eliminated antimalarials, shorter courses of treatment (3 days) are effective. The evidence of their superiority in comparison to monotherapies has been clearly documented. Artemisinin derivatives are safe and most effective against all stages of P.falciparum parasites. Since oral route of administration is most convenient in uncomplicated malaria patients, artesunate is the drug of choice amongst all available artemisinin derivatives. Curcumin has tested antimalarial activity in vitro and in experimental animals. It is also safe and economical. While elimination half time of artesunate is about minutes (artesunate + dihydroartemisinin), elimination half time of curcumin is about 4-6 hours, which can be prolonged further by addition of bioenhancers. Further, combination of antimalarials with different modes of action is twofold: (1) the combination is often more effective; and (2) in the rare event that a mutant parasite that is resistant to one of the drugs arises de novo during the course of the infection, the parasite will be killed by the other drug. A rationale for co-administration of artemisinin and curcumin (as a constituent of turmeric), is based on the fact that they are in human use for a long time. Curcumin is non-toxic and doses as high as 8 g/day for 3 months did not result in toxicity in a phase I clinical trial. No resistance has been reported against curcumin or artemisinin.21 A curcumin and artemisinin combination can lead to lower consumption of artemisinin and a decrease in the cost of the combination therapy compared to that with coartem. Curcumin is very effective in preventing recrudescence due to artemisinin monotherapy. Therefore this Phase 1 study has been planned to assess safety, tolerability and pharmacokinetics of artesunate with curcumin or biocurcumax co-administration. page 5 / 5