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Toxicological information

Carcinogenicity

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Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
other information

Data source

Reference
Reference Type:
other: EPAR Scientific discussion
Title:
Viread - EPAR Scientific discussion
Year:
2006
Bibliographic source:
European Medicines Agency

Materials and methods

GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
for 2 years.
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
The high doses in these studies were selected based on the endpoint of gastrointestinal/kidney/bone toxicity in the rat (0, 30, 100, 300 mg/kg)
Basis:

Control animals:
no

Results and discussion

Any other information on results incl. tables

Preliminary results (12 months and 22 months data in mice and rats) did not raise any particular concerns since no external gross evidence of carcinogenicity was reported.

Applicant's summary and conclusion

Conclusions:
Final report on the 104-week oral carcinogenicity study in rats:
In rats, no evidence of carcinogenicity in long-term oral studies at 5 times therapeutic dose in humans.
Lifetime daily administration of tenofovir DF at dosage levels of up to 300 mg/kg/day to Sprague-Dawley rats did not reveal major concerns in carcinogenicity. Nevertheless, an increased incidence of the sub-cutaneous tissue/lipoma in males and uterus polyp/endometrial stroma in females have been observed. In the light of historical control data, it was concluded that the 5% incidence of subcutaneous tissue/lipoma in male could be considered incidental in origin. Furthermore, based on the fact that the increase in uterus polyp/endometrial stroma in females was minimal compared to reported values and that there was no evidence of any treatment-related effect (non-neoplastic and neoplastic) on the reproductive organs (uterus, ovaries and vagina), the increase in incidence of the benign tumour could be considered to be of no toxicological significance.
In conclusion, given the results from the rat carcinogenicity assay, which the fact that tenofovir DF is positive only at the highest dose tested (600
carcinogenicity study, the margin of safety and the likelihood that the observed from local high concentrations of tenofovir DF, it can be considered that concerns, regarding the carcinogenic potential of tenofovir DF in patients.