Quetiapine XR for
the Schizophrenia
Dr Mohammad AlQurashi
Iraq
www.axantia.com
FGAs vs SGAs
FGAs
Efficacy
Tolerability
Positive symptoms
Extrapyramidal symptoms (EPS)
Relapse prevention
Tardive dyskinesia
Hyperprolactinaemia
SGAs*
Positive symptoms
Hyperglycemia
Negative symptoms
Weight gain
Cognitive symptoms
Mood symptoms
Relapse prevention
May provide neuroprotection
SGAs are replacing FGAs as first-line treatments in many countries
* Tolerability profiles of SGAs vary according to individual
antipsychotic
Tandon R & Jibson MD, 2003; Van Haren NE et al, 2007.
2
Relapse Rates Favour SGAs Over FGAs
(1-year Studies)
FGA
SGA
n/N
%
n/N
%
2/33
Csernansky 2000 - risperidone 41/177
6
23
3/30
65/188
10
35
Risperidone pooled
Daniel 1998 - sertindole
43/210
2/94
21
2
68/218
12/109
31
11
Speller 1997 - amisulpride
5/29
17
9/31
29
Tamminga 1993 - clozapine
1/25
4
0/14
0
Essock 1996 - clozapine
13/76
17
15/48
31
Rosenheck 1999 - clozapine
10/35
29
4/14
29
Clozapine pooled
24/136
18
19/76
25
Tran 1998a - olanzapine
10/45
22
2/10
20
Tran 1998b - olanzapine
6/48
13
3/14
21
Tran 1998c - olanzapine
71/534
13
29/156
19
Olanzapine pooled
87/627
14
34/180
19
Total
161/1096
15
142/614
23
Marder 2002 - risperidone
Overall analysis, P=0.0001 in favour of SGAs
Leucht S et al, 2003.
Risk difference
(95% CI fixed)
-0.6
Favours
SGA
0.6
Favours
FGA
3
What Is Quetiapine XR?
Hydration & Gel Formation
Hydrated Gel Layer
Water Channel
Hard Core
Quetiapine XR is released from the hard core over a 20-hour period
Data on file, DA-SXR-01; Data on file, DA-SXR-02.
4
Quetiapine XR:
Usual Target Dose is 600 mg/d
800
600 mg/d
Dose (mg)
600
400
300 mg/d
200
0
Day 1
Day 2
Dose can be increased to 800 mg after Day 2 depending on the response of the
patient
1. AstraZeneca Pharmaceuticals PI, USA; 2. AstraZeneca Pharmaceuticals SmPC, Netherlands.
5
Trial 132 (6 weeks)
PANSS Positive Subscale: At Day 42
Seroquel XR
600 mg
(n=111)
Seroquel XR
800 mg
(n=117)
Seroquel IR
400 mg
(n=119)
Improvement
LSM
change
from
baseline
Placebo
(n=115)
Seroquel XR
400 mg
(n=111)
#
#
#
#
#Treatment
groups that separated from placebo based on 95% confidence intervals
Seroquel XR has been approved for the treatment of Schizophrenia in some markets, and is currently under
regulatory review in others – Please check local prescribing information before use
MITT, LOCF
6
Trial 132 (6 weeks)
PANSS Negative Subscale: At Day 42
LSM
change
from
baseline
0
Placebo
(n=115)
Seroquel XR
400 mg
(n=111)
Seroquel XR
600 mg
(n=111)
Seroquel XR
800 mg
(n=117)
Seroquel IR
400 mg
(n=119)
-1
-2
Improvement
-3
-4
-5
-6
#
-7
#
#Treatment
-8
groups that separated from placebo based on 95% confidence intervals
MITT, LOCF
Seroquel XR has been approved for the treatment of Schizophrenia in some markets, and is currently under
regulatory review in others – Please check local prescribing information before use
7
5/19/2021 6:30 AM
ASERO XR
8
5/19/2021 6:30 AM
Time to Relapse After Randomization
Quetiapine XR Study 004
Survival distribution function
1.00
Quetiapine XR
(n=94)
0.75
Hazard Ratio:
0.13; 95% CI 0.07, 0.26; P<0.001
Relapse rates:
11.7% quetiapine XR; 48.5%
placebo
0.50
0.25
Placebo
(n=103)
0.00
0
2
4
6
Time (months)
8
10
Kaplan-Meier Survival Distribution Function shows the proportion of patients remaining relapse-free over time
Total ITT
Peuskens J et al, 2007.
ASERO XR
9
5/19/2021 6:30 AM
ASERO XR
10
Trial 041: Primary Outcome
5/19/2021 6:30 AM
In-house data, AstraZeneca Pharmaceuticals, LP.
LSM change from baseline in PANSS total score
• Only quetiapine
XR 600 mg/d
significantly
separated from
placebo on the
primary end point
XR XR XR IR IR
PBO 300 600 800 300 600
(78) (83) (87) (85) (85) (80)
0
-4
-8
-12
*
-16
ASERO XR
*P<0.05 vs placebo
MITT, LOCF
11
QUETIAPINE XR
Asero XR delivers:
•
Acute efficacy
–
•
•
Maintenance of efficacy
–
Prevention of relapse
–
Significantly reduced risk of relapse
Trusted tolerability
–
•
5/19/2021 6:30 AM
On the core symptoms of Schizophrenia
In the acute setting and over longer term treatment
Ease of use
–
Once daily dosing
–
2–3 day-dose escalation
–
Effective dose range by Day 2
–
Clear target dose
–
Same dose for initiation and maintenance
ASERO XR
12
Trial 132/Trial 133/Trial 041 (6 weeks)
Incidence of Adverse Events and Withdrawals Due
to Adverse Events
Placebo
(n=319)
Seroquel XR
(n=951)
Seroquel IR
(n=414)
All adverse events
61.4
69.5
72.5
Serious adverse events
4.4
4.4
3.9
0
0
0.2
30.7
43.3
45.9
7.5
6.4
7.7
Patients, %
Deaths
Drug-related adverse
events
Discontinuation due to
adverse events
5/19/2021 6:30 AM
ASERO XR
Pooled Safety
Population
13
Trial 132 (6 weeks)
Incidence of Adverse Events
Seroquel XR
Patients, n (%)
Placebo
(n=118)
400 mg
(n=113)
600 mg
(n=113)
800 mg
(n=121)
Seroquel IR
400 mg
(n=123)
Any AE
50 (42.4)
51 (45.1)
62 (54.9)
56 (46.3)
66 (53.7)
2 (1.7)
2 (1.8)
3 (2.7)
1 (0.8)
6 (4.9)
0 (0)
0 (0)
0 (0)
0 (0)
1 (0.8)
15 (12.7)
23 (20.4)
34 (30.1)
27 (22.3)
27 (22.0)
3 (2.5)
6 (5.3)
3 (2.7)
3 (2.5)
6 (4.9)
Serious AEs
Deaths
Drug-related AEs
Discontinuations due
to AEs
Safety
Population
5/19/2021 6:30 AM
ASERO XR
14
Trial 004 (16-week open-label, randomized duration mean 4 months, maximum 9 months)
Incidence of Adverse Events
Stabilization Phase
Patients (%)
All adverse events
Randomization Phase
Open-label Seroquel XR Placebo Seroquel XR
(n=327)
(n=103)
(n=94)
49.8
40.8
31.9
0
1.9
0
Drug-related AE
40.7
21.4
18.1
Adverse events leading
to discontinuation
1.2
1.0
1.1
3.4
1.0
1.1
Serious adverse events
EPS-related adverse
events
Safety
Population
5/19/2021 6:30 AM
ASERO XR
15
Pooled Safety
Population
Trial 132/Trial 133/Trial 041 (6 weeks)
Common Adverse Events
(>5% Patients in Any Treatment Group)
Placebo
(n=319)
Seroquel XR
(n=951)
Seroquel IR
(n=414)
Sedation
6.6
12.7
15.7
Dry mouth
1.3
12.1
9.2
Somnolence
3.8
12.1
13.3
Dizziness
3.8
9.8
8.9
Headache
14.7
9.7
10.1
Insomnia
14.4
7.5
6.8
Orthostatic hypotension
4.7
7.4
9.4
Constipation
4.7
6.4
6.0
Nausea
6.9
5.5
4.6
Dyspepsia
2.2
4.6
4.8
Agitation
5.0
3.7
3.4
Tachycardia
0.9
2.8
6.3
Patients, %
5/19/2021 6:30 AM
ASERO XR
16
Trial 132/Trial 133/Trial 041 (6 weeks)
Adverse Events Related to Somnolence or Postural
Hypotension
Placebo
(n=319)
Seroquel XR
(n=951)
Seroquel IR
(n=414)
Any somnolencerelated AEs
10.3
25.0
29.5
Any postural
hypotensionrelated AEs
5.6
8.5
10.1
Patients, %
*Somnolence cluster includes the MedDRA-preferred terms: somnolence, sedation,
lethargy, and sluggishness
**Postural hypotension cluster includes the MedDRA-preferred terms: dizziness postural,
orthostatic hypotension, and orthostatic hypotension tachycardia syndrome
Patients with multiple events are only counted once
Pooled Safety
Population
5/19/2021 6:30 AM
ASERO XR
17
Trial 132/Trial 133/Trial 041 (6 weeks)
EPS-related Adverse Events
• Incidence of any EPS-related AEs was 4.7% with
placebo, 7.5% with Seroquel XR and 7.7% with
Seroquel IR
• No individual EPS item occurred in >2% of patients
treated with Seroquel XR, eg:
Placebo
(n=319)
Seroquel XR
(n=951)
Seroquel IR
(n=414)
Akathisia
1.3
1.8
2.4
Extrapyramidal
disorder
1.6
1.2
1.0
0
0.5
0.5
0.3
0.3
1.0
Patients, %
Dystonia
Dyskinesia
Pooled Safety
Seroquel XR has been approved for the treatment
of Schizophrenia
in some markets, and is
Population
5/19/2021 6:30 AM
ASERO
XR
currently under regulatory review in others – Please check local prescribing information before use
18
Trial 132/Trial 133/Trial 041 (6 weeks)
Change in Weight
Placebo
(n=319)
Seroquel XR Seroquel IR
(n=951)
(n=414)
Mean change, kg
0.2
1.3
1.4
≥7% increase in weight, %
5.4
9.9
12.5
Pooled Safety
Population
5/19/2021 6:30 AM
Seroquel XR has been approved for theASERO
treatment
XR of Schizophrenia in some markets, and is
currently under regulatory review in others – Please check local prescribing information before use
19
Trial 132 establishes that the effective dose range of Seroquel XR
once daily for acute schizophrenia is 400–800 mg/day
In all the Seroquel XR trials (except Trial 041) patients received
either 400 mg or 600 mg by Day 2
Trial
5/19/2021 6:30 AM
Day 1
Day 2
Day 3
132
300
400
600
400
600
800
004
300
600
400-800
146
300
600
400
600
800
147
300
600
400 - 800
Seroquel XR has been approved for theASERO
treatment
XR of Schizophrenia in some markets, and is
currently under regulatory review in others – Please check local prescribing information before use
20
FDA APPROVED
• Acute schizophrenia from age 13
• Schizophrenia maintenance
5/19/2021 6:30 AM
ASERO XR
21
Summary
• QUETIAPINE XR once daily demonstrates significant efficacy across a broad
range of symptoms including core symptoms of acute schizophrenia
• Seroquel XR once daily is effective in preventing relapse in stable patients
with chronic schizophrenia
• Seroquel XR once daily is well tolerated across the dose range and over
longer term treatment
(up to 9 months)
• once daily can be prescribed at the therapeutically effective dose range by
Day 2 and does not need to be adjusted for maintenance treatment
5/19/2021 6:30 AM
Seroquel XR has been approved for theASERO
treatment
XR of Schizophrenia in some markets, and is
currently under regulatory review in others – Please check local prescribing information before use
22
Overall Conclusions
of ASERO XR
• The PK profile of quetiapine XR provides smoother, more stable plasma concentrations
than Seroquel IR
• Once daily at doses of 400–800 mg/day is effective in the treatment of acute
schizophrenia
• The therapeutic dose range is reached by Day 2 with once daily
• It is effective in preventing relapse in patients with chronic stable schizophrenia
• Patients can be easily switched from IR to XR without deterioration of clinical
condition
• Patients can be easily switched from other antipsychotics to ASERO XR using a 4-day
cross-titration period
• Once daily Seroquel XR is well tolerated and the overall safety profile is similar to
Seroquel IR
5/19/2021 6:30 AM
ASERO XR
23
Thank You
www.axantia.com