Transcript Ingen diastitel

Evaluation of a new drug
A new drug?
Cipramil: R- and S-citalopram
Cipralex: S-citalopram
In-vitro results
Owens MJ et al.:
•
S-citalopram was an approx. 30-fold more potent inhibitor of
the serotonin transporter than R-citalopram
•
S-citalopram was the most serotonin transporter selective
compound when tested against all other marketed SSRI’s
Other tests:
• Bioavailability, metabolism and elimination
• Interconversion between R- and S-form
• Activity of metabolites
Conclusion:
• The majority of the therapeutic activity propably
resides in the S-form
Clinical effect
Four clinical studies have been submitted:
Wade et al.:
Cipralex vs. placebo
Cipralex sign. better than
placebo
Burke et al.:
Cipralex vs. Cipramil
and placebo
Cipralex and Cipramil
sign. better than placebo
No difference between
active treatments
Montgomery et al.: Cipralex vs.
Cipramil and placebo
Cipralex sign. better than
placebo. No difference
Cipramil and placebo
MD-02:
No difference between
active treatments and
placebo
Cipralex vs. Cipramil
and placebo
Clinical effect
Study
Number
of patients
Treatments
Wade et al.
380
Esc. 10 mg
Placebo
Escitalopram was significantly more effective than
placebo
Burke et al.
485
Esc. 10 mg
Esc. 20 mg
Cit. 20 mg
Cit. 40 mg
Placebo
The active treatments were
all signficantly more effective than placebo. No
significant differences
were found neither between
cit. 40 mg and esc. 10 mg nor
between cit. 40 mg and esc.
20 mg
Data after 4 weeks of
treatment showed, that escitalopram was significantly more effective than
placebo. No significant differences were found between
placebo and citalopram.
Montgomery et al.
486
Esc. 10 mg
Cit. 20 mg
Placebo
MD-20
386
Esc. 10-20 mg
(flexible dose)
Cit. 20-40 mg
(flexible)
Placebo
Results
Neither escitaslopram nor
citalopram was more effective than placebo. The
study has been classified
as a failure
The advantage of pooling
data...
Gorman JM et al.
2002:
The advantage of pooling
data...
Tabel 2. LOCF values by visit for the major efficacy parameters: MADRS and CGI-I
Study WeekPlacebo
MADRS
1
2
4
6
8
Escitalopram
Citalopram
-3.8
-6.6
-9.4
-10.3
-11.2
-4.7* +
-7.8 *
-11.0*
-13.0* +
-13.8*
-3.7
-7.2
-10.2
-12.0*
-13.1*
MADRS-severe
1
2
4
6
8
-4.2
-7.4
-10.4
-11.7
-12.2
-5.5* +
-9.0*
-12.2*
-14.7* +
-16.2* +
-4.3
-7.9
-11.3
-12.8
-14.3
CGI-I
1
2
4
6
8
3.5
3.2
2.9
2.8
2.7
3.3*
3.0*
2.6*
2.4*
2.1*
3.4
3.1
2.7*
2.5*
2.3*
Gorman JM et al. 2002
Choosing statistical analysis...
Gorman JM et al., 2002:
Choosing statistical analysis...
Gorman JM et al., 2002:
Conclusion - company
•
Cipralex provides an early ease of symptoms
•
Cipralex has a significantly better effect compared
to Cipramil - also at severe depression
•
Cipralex is the most selective SSRI
•
Cipralex is well-tolerated with a safety-profile
similar to that of Cipramil
Conclusion - IRF
It has not been shown that Cipralex has
any clear cut advantages compared to
Cipramil.
Next morning...