Delving into the Latest Updates on DRL-17822 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CETP

Mechanism

CETP inhibitors(Cholesteryl ester transfer protein inhibitors)

Therapeutic Areas

Congenital DisordersEndocrinology and Metabolic DiseaseCardiovascular Diseases

Active Indication-

Inactive Indication

AtherosclerosisDyslipidemiasHypercholesterolemia+ [1]

Originator Organization

Dr. Reddy's Laboratories Ltd.

Active Organization-

Inactive Organization

Dr. Reddy's Laboratories Ltd. (Russia)Dr. Reddys Laboratories Tennessee LLC

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC30H31F6N7

InChIKeyOCNBSSLDAIWTKS-UHFFFAOYSA-N

CAS Registry898911-09-6

We aimed to characterise the population pharmacokinetics of cholesteryl ester transferase protein inhibitor DRL‐17822 in healthy males and explore the effect of food and formulation on the oral absorption of DRL‐17822 in 4 phase I studies. DRL‐17822 was dosed orally (2–1000 mg) in 2 different drug formulations (nanocrystal formulation and amorphous solid dispersion formulation) after either an overnight fast, or a low‐fat, continental or high‐fat breakfast. A 2‐compartment model with 6 transit absorption compartments best characterised the data. Additionally, a strong interaction of food and formulation on bioavailability was observed and parsimoniously characterised in the model by binning combinations of food state and formulation with similar bio‐availabilities. The final model adequately characterised the pharmacokinetic data of DRL‐17822 in healthy males including the complex interaction of food and drug formulation. The amorphous solid dispersion formulation has a lower food effect on bioavailability compared with the nanocrystal formulation.

01 Nov 2019·Clinical Pharmacology in Drug Development

Effect of Food on the Pharmacokinetics of 2 Formulations of DRL‐17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males

Article

Author: Gandhi, Rajesh ; Burggraaf, Jacobus ; de Kam, Marieke L. ; Kamerling, Ingrid M.C. ; Stevens, Jasper ; Kulkarni, Swati ; Gautam, Anirudh ; Raghuvanshi, Rajeev S. ; Padhi, Bijay K. ; Kumar, Rajinder ; Alikunju, Shanavas ; Kruithof, Annelieke C.

AbstractDRL‐17822 is a novel selective cholesteryl ester transfer protein inhibitor that showed an increased exposure, including an increase of >20‐fold of maximum concentration and area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration, following a high‐fat breakfast using a nanocrystal formulation. To reduce this effect of food, we generated an amorphous solid dispersion formulation. In this study, we compared the food effect of both formulations of DRL‐17822 in a 2‐part randomized, open‐label, 4‐way crossover study involving healthy adult males 18‐45 years of age. In both parts of the study, 12 subjects received both formulations of DRL‐17822 in both the fasted and fed states; a low‐fat breakfast was provided in the first part and a high‐fat breakfast in the second part. Compared to the nanocrystal formulation, the amorphous solid dispersion formulation substantially increased DRL‐17822 exposure in the fasted state, including increased maximum concentration, area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration, and area under plasma concentration–time curve from time zero to infinity. Following a high‐fat breakfast, DRL‐17822 exposure was increased to a lesser extent in the amorphous solid dispersion formulation compared to the nanocrystal formulation (P < .001). Moreover, compared to the nanocrystal formulation the amorphous solid dispersion formulation caused a more pronounced increase in high‐density lipoprotein in the fasted state. Consuming breakfast increased the effect of DRL‐17822 on high‐density lipoprotein. Taken together, our results indicate that by improving its formulation, DRL‐17822 has a favorable exposure profile and therefore a more predictable food effect profile.

01 Jan 2010·Drugs of the FutureQ4 · MEDICINE

High-density lipoprotein modulation targets

Q4 · MEDICINE

Article

Author: Mousa, S. S. ; Block, R. C. ; Mousa, S. A.

Given the strong genetic determinants of favorable HDL-C levels, the ability to procure the cardiovascular disease and longevity benefits associated with this mediator of the reverse cholesterol transport pathway through pharmaceutical intervention is challenging. Niacin is still the most robust HDL-C raising pharmaceutical agent on the market at its use leads to elevations up to 35%. Cholesteryl ester transfer protein (CETP) and endothelial lipase (EL) are two targets involved in the reverse cholesterol transport pathway that have become therapeutic targets of various investigations for raising HDL. However, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial was stopped in December 2006 due to excess mortality in the group of patients treated with torcetrapib, a CETP inhibitor. Other CETP inhibitors being studied include anacetrapib and JTT-705. Other CEPT inhibitors including TA-8995, DRL-17822, JTT-302, and others are under investigation. Additionally a biologic target CETi-1, an investigational vaccine in phase II development designed to elicit antibodies that bind and inhibit the activity of CETP leading to blocking the ability of the protein to transfer cholesterol from HDL to LDL and thus causing HDL cholesterol levels to rise is under clinical investigation for sometime.

100 Deals associated with DRL-17822

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipoproteinemia Type II	Phase 3	PL	Dr. Reddy's Laboratories Ltd. (Russia)	01 Jul 2011
Hyperlipoproteinemia Type II	Phase 3	IT	Dr. Reddy's Laboratories Ltd. (Russia)	01 Jul 2011
Hyperlipoproteinemia Type II	Phase 3	UA	Dr. Reddy's Laboratories Ltd. (Russia)	01 Jul 2011
Hypercholesterolemia	Phase 2	IT	Dr. Reddy's Laboratories Ltd. (Russia)	01 Jul 2011
Hypercholesterolemia	Phase 2	PL	Dr. Reddy's Laboratories Ltd. (Russia)	01 Jul 2011
Hypercholesterolemia	Phase 2	UA	Dr. Reddy's Laboratories Ltd. (Russia)	01 Jul 2011
Atherosclerosis	Phase 2	IN	Dr. Reddys Laboratories Tennessee LLC	-
Dyslipidemias	Phase 2	IN	Dr. Reddys Laboratories Tennessee LLC	-