Study identification

PURI

https://redirect.ema.europa.eu/resource/1000000369

EU PAS number

EUPAS1000000369

Study ID

1000000369

Official title and acronym

DARWIN EU® - Association between genetic polymorphisms of interest and risk of myopathy among statin users

DARWIN EU® study

Yes

Study countries

Estonia
United Kingdom

Study description

Around 1% to 30% of statin users report mild muscle symptoms including pain and/or weakness, usually
without significant creatine kinase (CK) elevation. Severe myopathy (CK elevation <10 times normal) occurs
in 0.1% of cases, while rhabdomyolysis (>40 times normal CK) is even rarer (<0.01%).
There is current regulatory interest in exploring the role the OATP1B1 (SLCO1B1 c.521CC) gene
polymorphism in atorvastatin users (treated with a fixed dose combination of acetylsalicylic acid/atorvastatin/ramipril) with regards to the risk of myopathy. SLCO1B1 encodes the liver-expressed OATP1B1
protein, which clears statins like rosuvastatin, atorvastatin, simvastatin, and pravastatin from the blood.
The SLCO1B1 521T>C polymorphism (rs4149056) reduces hepatic clearance of these statins, with
simvastatin being most affected, and fluvastatin and rosuvastatin less so. Atorvastatin, a first-line lipid
lowering drug for cardiovascular disease, is widely prescribed but often discontinued due to muscle
complaints.
More broadly, the aim of this study is to inform whether genetic testing could help predict the risk of
myopathy in users of atorvastatin and other selected statins, and whether dose adjustment would help
minimise risk for carriers of known polymorphisms. In addition, this study serves as a proof-of-concept of
the capacity of DARWIN EU to generate pharmacogenomic evidence to support regulatory decision making.

Study status

Ongoing
Research institutions and networks

Institutions

Networks

Contact details

Junqing Xie

Primary lead investigator
Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

Planned:
Actual:

Date of final study report

Planned:
Sources of funding
EMA
Study protocol
Initial protocol

DARWIN EU_Protocol_P3-C3-004_Statins_V6.pdf

English (775.56 KB - PDF)View document
Regulatory

Was the study required by a regulatory body?

Yes

Is the study required by a Risk Management Plan (RMP)?

Not applicable