Highlights

image01 Synthetic molecule (Artemesinine Derivative).

image01 Pre-Clinical Studies completed.

image01 Pharmacologically safe, effective & Toxicologically safe.

image01 Clinical Trial permission from DCGI to carry out Phase-I studies.

image01 Phase-I Single dose clinical trial in normal healthy volunteers already completed along with human single dose pharmacokinetic studies.

image01 Safe in Phase-I single dose studies in normal healthy volunteers.

Preamble

Malaria is one of the most widespread tropical parasitic diseases, caused by the protozoa of the genius plasmodium and transmitted by the female anopheles mosquito. According to the world malaria report 2011 of the World Health Organization (WHO), there were 216 million cases of malaria in the world in 2010. As much as 81% of these were in Africa and 13% is South-East Asia. There were an estimated 655,000 deaths in that year. Most of the deaths occurred in sub-Saharan Africa and the victims were mostly children under the age of five. Malaria remains the major public health problem in India . Northeastern region of India is one of the hot spots for malaria transmission. Focal outbreaks of malaria are of common occurrence especially in forest-fringed villages of Assam, bordering Arunachal Pradesh. Orissa alone contributes to more than 40% of P. falciparum deaths in India; south Orissa is a known as hyper-endemic area of the state.

Commonly used drugs to treat malaria are quinine (1), chloroquine (2) mefloquine (3), amodiaquine (4), primaquine (5), artemisinine (6), piperquine (7) dapsone (8) and sulfadiazine (9). But the rapidly increasing resistance of P. falciparum malaria parasites to drugs such as quinine, chloroquine, proguanil and pyrimethamine has made malaria chemotherapy ineffective. Most widely used antimalarial drugs, chloroquine (CQ) is a 4-aminoquinoline is the gold standard for the treatment of malaria that was previously characterized by its efficacy and low toxicity. But now malaria parasite developed resistance to Chloroquine with complex point mutations in the gene encoding PfCRT ultimately enhances efflux of Chloroquine from the food vacuole resulting low concentration of drug which makes the drug ineffective. Literature strongly suggests the involvement of compound specific resistance. To overcome the challenges in malaria chemotherapy in view of the fast growing resistance against existing drugs, there is an urgent need to develop new drugs. Structural modification of existing drugs offers promise for the development of new drugs as their mechanism of action, pharmacokinetic and toxicity profiles are already known.

Current Status

CDRI Comp 97/78 is a trioxane peroxide, a synthetic derivative of artemesinin. Pre-clinical regulatory studies have been completed. It is found safe in preclinical regulatory pharmacology and toxicity studies. DCGI permission to carry out phase-I clinical trial and pharmacokinetic studies has been obtained.

Phase-I single dose studies have been completed in PGIMER, Chandigarh and found safe and well-tolerated in normal healthy subjects. PK studies in normal healthy subjects in single dose shows rapid absorption and rapid conversion to its precursor 97/63; this confirmed preclinical data on the molecule. The higher t1/2 may help maintain the therapeutic efficacy and reduce the occurrence of recrudescence of malarial parasite during therapy and follow-up.

Patent Status
Title Inventor(s) Application Number Filing  Date Patent Number Date of Grant
An improved process for the preparation of ether derivatives of dihydroartemisinin Chandan Singh & Rani Kanchan 1258DEL1997 13-May-97 186127 25-Jan-02
Novel substituted 1,2,4- trioxanes useful as antimalarial agents Chandan Singh & Sunil Kumar Puri 1579DEL1999 28-Dec-99 232539 18-Mar-09
BD-0058/2000 31-Mar-00 1003409/2000  
ID-P-20000261 31-Mar-00 ID0011878 13-Oct-03
ML-PI-20001330 31-Mar-00    
PK-819/2001 DIV 22-Aug-01    
PK-0288/2000 31-Mar-00 137301 31-Jul-02
SG-200001862-2 31-Mar-00    
SL-200001862.2 31-Mar-00 0084585 30-Sep-04
LK-12044 31-Mar-00 12044 27-Oct-00
TH-056618 31-Mar-00    
US-09/539574 31-Mar-00 6316493 13-Nov-01
Vl-S20000281 31-Mar-00
VN-S20000281 31-Mar-00 4230 13-Apr-04
ZA-2000/1642 31-Mar-00 2000/1642 27-Dec-00