Registration Dossier

Administrative data

Endpoint:
reproductive toxicity, other
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
The information has been assessed and approved by the European Medicines Agency

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Principles of method if other than guideline:
Testing in accordance to requirements for approval of medicines
GLP compliance:
not specified
Remarks:
Attached document is a summary of EMEA registration based on animal studies for registration of pharmaceutical product, thus GLP compliance most likely but not specified in document.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Molecular formula: C172H265N43O51
Molecular weight (MW): 3751.2 Da
Specific details on test material used for the study:
Liraglutide

Test animals

Species:
other: rat and rabbits

Administration / exposure

Route of administration:
subcutaneous

Results and discussion

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:
not determinable

Results: F1 generation

Effect levels (F1)

Remarks on result:
not determinable

Overall reproductive toxicity

Reproductive effects observed:
no
Treatment related:
no

Any other information on results incl. tables

EMEA summary data available (see attached document below):

Animal studies using subcutaneous injections of liraglutide did not indicate direct harmful effects with respect to fertility but slightly increased early embryonic deaths at the highest dose. Dosing with Victoza during mid-gestation caused a reduction in maternal weight and foetal growth with equivocal effects on ribs in rats and skeletal variation in the rabbit. Neonatal growth was reduced in rats while exposed to Victoza, and persisted in the post-weaning period in the high dose group. It is unknown whether the reduced pup growth is caused by reduced pup milk intake due to a direct GLP1 effect or reduced maternal milk production due to decreased caloric intake.

Thus, when making read-across of the liraglutide (API) data set to liraglutide precusor (T), the substance is not to be classified for effects on fertility and development according to the CLP-criteria.

Applicant's summary and conclusion

Conclusions:
Data on reprodutive toxicity using subcutaneous injection of liraglutide indicate that liraglutide as a GLP1 agonist may induce reprotox effects as a secondary effects in relation to body weight loss and reduces intake of calories. No direct reprotoxic effects are indicated.

Thus, when making read- across of the data to liraglutide precusor the substance is not to be classified for effects on fertility and development according to the CLP-criteria.
Executive summary:

Animal studies using subcutaneous injections of liraglutide did not indicate direct harmful effects with respect to fertility but slightly increased early embryonic deaths at the highest dose. Dosing with Victoza during mid-gestation caused a reduction in maternal weight and foetal growth with equivocal effects on ribs in rats and skeletal variation in the rabbit. Neonatal growth was reduced in rats while exposed to Victoza, and persisted in the post-weaning period in the high dose group. It is unknown whether the reduced pup growth is caused by reduced pup milk intake due to a direct GLP1 effect or reduced maternal milk production due to decreased caloric intake.