ongoing

E1508I0242. The following post authorisation
measure is fulfilled:
PAM 8: The Applicant is requested to investigate
the CYP induction potential of ospemifene at
clinically relevant intestinal concentrations to
exclude potential CYP3A4 induction in the
intestine. No CYP induction is expected for
ospemifene and M-1 at clinically relevant
systemic concentrations.
-Update of section 5.2 of the SmPC in order to
update the elimination section of the SmPC as a
result of the submission of study E1508I0242 to
fulfil the following post authorisation measures:
PAM 13: The applicant committed to evaluate
and the conversion of the Z-enantiomer of
ospemifene to its E-enantiomer post marketing.
PAM 14: The applicant committed to evaluate
the metabolism and excretion of ospemifene
and its metabolites using the commercial
ospemifene 60 mg under fed conditions in a
postauthorization study.
-Update of section 5.2 of the SmPC in order to
update the distribution section as a result of the
submission of study OSP-PF-046-N and OSP-PF-
047-N to fulfil the following post authorisation
measures:
PAM 6: The in vitro plasma protein binding data
of M-1 in the non-clinical species will be
provided post-authorisation for interspecies
comparison between non-clinical species and
humans. However the protocol should be
adapted; the Applicant is requested to
investigate a concentration range, e.g. 50 to
200 ng/mL for M1.
PAM 7: The blood-to-plasma ratio data for
ospemifene in monkey and rat and the blood-to
plasma ratio for M-1 in rat, monkey and human
will be provided post-authorisation.
However the protocol should be adapted; the
Applicant is requested to investigate a
concentration range, e.g. 500 to 1200 ng/mL for
ospemifene and 50 to 200 ng/mL for M 1.
-Update of section 5.2 of the SmPC in order to
update the biotransformation section as a result
of the submission of study OSP-PF-041-N to
fulfil the following post authorisation measure:
PAM 9: The Applicant will provide BSEP
transporter studies post-marketing.
As a consequence, an updated RMP version 1.2
Annex to December 2016 CHMP Agenda
EMA/CHMP/819197/2016 Page 35/55