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The
Parkinson-REGAIN study
Early Piribedil in monotherapy of Parkinson’s
disease.
7 months’ result
2-year result
The Parkinson-RESTORE study
A multicenter
trial of Trivastal L.A. as early adjunct treatment for
Parkinson's disease.
Safety and efficacy
of Trivastal L.A. as adjunctive treatment for Parkinson’s
disease – 6-month placebo-controlled study.
12-month safety
of piribedil as early adjunct treatment in Parkinson's
disease. Piribedil international follow up study.
The Parkinson-CONTROL study
A multicenter
trial comparing piribedil (Trivastal L.A., 3 tablets/day)
to bromocriptine (25 mg/day) in early combination with
L-dopa in Parkinson’s disease
1-year results
2-year results
Trivastal retard's 50 effects on
parkinsonian cognitive dysfunction compared with bromocriptine
in early combination with L-dopa |
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| The Parkinson-REGAIN
study |
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Early
piribedil monotherapy of Parkinson’s disease.
A planned 7-month interim report of a 2-year controlled
study. The Parkinson Regain Study. |
7 months’ result
Rascol O, Castro Caldas A, Dubois B,t al. Arch Neurol.
In press. |
AIM
The Parkinson-REGAIN study, an international multicenter
study, is currently ongoing to evaluate Trivastal retard
50’s efficacy in monotherapy as first-line treatment
in newly diagnosed parkinsonian patients. The major
objective of the study was to evaluate the improvement
in motor symptoms (UPDRS III) after 7 months of treatment,
and the long-term (24 months) occurrence of motor complications
such as dyskinesia and motor fluctuations. |
| METHOD
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The
Parkinson-REGAIN study is a 2-year, international, multicenter,
double-blind, placebo controlled parallel group study.
Of the 401 randomized patients (mean age 62.3±9.9),
386 patients were included in the ITT analysis (199
placebo/187 Trivastal retard 50). Demographic characteristics
of the randomized patients were similar in both group.
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| RESULTS
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ITT
analysis of the last evaluation on monotherapy shows
a significant improvement in UPDRS III score with Trivastal
retard 50, whereas patients on placebo show a worsening
of this score (-4.9 vs + 2.6 respectively P<0.0001).
At the last evaluation on monotherapy,
more than 40% of patients on Trivastal retard 50 show
a decrease of at least 30% of their baseline UPDRS III
qcore, reflecting a strong treatment effect. More than
80% of patients are still on monotherapy after 6 months
of active treatment.
Figure 1: Trivastal retard 50 shows
a significant improvement in UPDRS III score (ITT, n=386).
At the last evaluation on monotherapy,
patients on Trivastal retard 50 show a significant decrease
of –1.2 (vs +1.5 on placebo) of activities of
daily living scores (UPDRS II), proving Trivastal retard
50’s efficacy on all aspects of the disease.
Trivastal retard 50 demonstrated a good safety profile
particularly with a low percentage of nausea (12%) compared
to placebo group (3.9%).
CONCLUSION
Results of the first 6 months of the
Parkinson-REGAIN study demonstrate that Trivastal retard
50 is effective and well tolerated as first-line monotherapy
in early stage Parkinson’s disease. |
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Two-year
results of the REGAIN study, a placebo-controlled trial
with the non-ergot dopamine agonist piribedil as early
treatment of Parkinson’s disease. |
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| Lees A,
Castro-Caldas A, Dubois B, et al. Presented at the congress
of the European Federation of Neurological Society in
September 2005, in Athens, Greece. |
| AIM
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To
assess, after a 24-month follow-up of the REGAIN study
(Rascol et al. Mov Disord. 2004; 19:S215) the occurrence
of motor complications while placebo double-blinding
was maintained.
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| METHOD
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401
de novo PD patients were randomized and 386 analyzed
in the full analysis set (FAS). Patients received adjustable
doses of piribedil (150-300 mg/d) or placebo for up
to 24 months. Open-label L-dopa adjunct was permitted
by Day 42. Time to motor complications was defined as
the first occurrence of either wearing-off, on/off or
dyskinesia (Cox model). Secondary endpoints included
L-Dopa sparing effect, UPDRS II, and UPDRS III (ANCOVA).
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| RESULTS
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L-Dopa sparing effect: 32% of patients randomized
to piribedil received L-dopa supplementation versus
64% on placebo
Low motor complication: In the FAS, there was no
difference in first occurrence of motor complications
between groups: 16.6% on piribedil versus 20.6% on
placebo. The same was true for fluctuations and dyskinesia
analyzed separately.
Efficacy on motor symptoms: both UPDRS II and UPDRS
III changes from baseline were in favor of piribedil
with respectively 0.9 points (P=0.067) and 3.49 (P<0.001;
post-hoc) estimated difference versus placebo (last
observation carried forward).
CONCLUSION
piribedil did not induce a greater risk of motor
complications while it demonstrated better control
of parkinsonian symptoms and spared the need for L-dopa.
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| The Parkinson-RESTORE
study |
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A
multicenter trial of Trivastal L.A. as early adjunct
treatment for Parkinson's disease. Piribedil International
Study Group (PISG). |
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Kwiecinski
H, Fedorova N, Takacs A, Ruzicka E, and Jamrozik Z.
Presented at the American Academy of Neurology congress,
Denver, USA, 2002. Neurology. 2002;58(suppl 3):A163.
After being widely assessed in Parkinson's
disease during the last 25 years in different countries,
Trivastal L.A. provides today new proof of its efficacy
in early combination with levodopa.
This international study involved 4 countries (Poland,
Russia, the Czech Republic, and Hungary), and 273 patients
with Parkinson's disease insufficiently controlled by
levodopa (≤600 mg/day). It was a randomized, double-blind,
placebo-controlled study with parallel groups to assess
Trivastal L.A., 3 tablets daily, over a 6-month treatment.
The primary end- point was the Unified Parkinson's Disease
Rating Scale motor score (UPDRS III) change versus Day-0
values. The secondary end- points included: comparison
of response rate (defined by a 30% decrease from baseline
of UPDRS III score), a description of L-dopa daily dose
change, UPDRS II score (Activities of Daily Living),
Hoehn and Yahr stage, Schwab and England score.
The results confirm the efficacy of Trivastal L.A. in
early combination in patients insufficiently controlled
by L-dopa. At 6 months:
The decrease in UPDRS III score from baseline was
significantly higher in the Trivastal L.A. group than
in placebo arm in the full analysis set (P<0.009)
and in per-protocol (P<0.006).
All the motor subscores were significantly improved:
tremor, rigidity, and bradykinesia.
Furthermore, Trivastal L.A. improved the activities
of daily living (UPDRS II), the Hoehn and Yahr stage,
and the Schawb and England score, showing that patients'
daily life was clinically improved.
The authors conclude that Trivastal L.A., 3 tablets
daily, is efficient and well-tolerated in early combination
with L-dopa when the latter remains insufficient to
restore motor functioning. |
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Safety
and efficacy of Trivastal L.A. as adjunctive treatment
for Parkinson’s disease – 6-month
placebo-controlled study. |
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| Fedorova
N, Jamrozik Z, Takats A, Ruzicka E, Del Signore S, Kwiecinski
H. Presented at the International Congress on Parkinson’s
Disease and Movement Disorders, Miami, USA, 2002. Mov
Disord. 2002;17(Suppl 5):S101-102.
New data on the Parkinson-RESTORE study
confirm Trivastal L.A., 3 tablets daily, therapeutic
value in early combination with levodopa, and especially
its good tolerance.
At 6 months, Trivastal L.A. significantly improved:
The UPDRS global motor score (P<0.05),
The sub-scores bradykinesia, rigidity, and posture
and gait (P<0.04),
The quality of daily living as demonstrated
by the UPDRS ADL score (P<0.001).
The Hoehn and Yahr stage improved more on Trivastal
L.A. than placebo (-0.38 versus –0.08, respectively).
Trivastal L.A. was well tolerated, and only 9 patients
withdrew due to an adverse event compared to 6 in the
control group (p=ns). No unintended sleep episodes were
reported.
The authors conclude that Trivastal L.A., 3 tablets
daily, is efficacious in early combination with L-dopa.
The favorable effect on posture and gait disorders may
be related to the α2-adrenergic receptor antagonist
properties of Trivastal L.A.. Moreover, Trivastal L.A.
was extremely well tolerated. |
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Federova
N, Ruzicka, E, Takats A et al. 12-month safety
of piribedil as early adjunct treatment in Parkinson's
disease. Piribedil international follow up study. |
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| New
data on the Parkinson-RESTORE study that confirm Trivastal
L.A., 3 tablets daily, therapeutic value in early combination
with levodopa, and especially its good tolerance after
12 months compared with placebo. Among 273 patients
insufficiently controlled by L-dopa and randomized in
a 6-month period, 147 carried on the study up to 12
months: 80 on Trivastal L.A., and 67 on placebo.
The follow-up of the whole population up to 12 months
showed 47% of patients on Trivastal L.A. and 42% on
placebo reported at least one emergent adverse effect
(AE). The most frequent AEs were gastrointestinal, such
as nausea with 8.1% on Trivastal L.A. and 2.9% on placebo
and anorexia with respectively 2.9% and 0.7%. Postural
hypotension was less frequent on Trivastal L.A.:
3.7% versus 5.1% on placebo. Among psychiatric symptoms,
depression was reported by 3.7% of patients on Trivastal
L.A. and 1.5% on placebo. Sleep-related symptoms
were infrequent: insomnia with 1.5% on Trivastal L.A.
and 3.6% on placebo and somnolence with respectively:
2.2% and 0.7%. No unintended sleep episodes were
reported. Fifteen serious adverse events were reported
in the whole study: six on Trivastal L.A. (one vertebral
fracture just before the inclusion, one erysipelas,
two thrombophlebitis, one bronchitis and one pancreatitis)
and nine on placebo (one traumatic shock, one fatigue,
one paresis, one cholangitis, one pancreatitis, one
tolerance decrease, one uterine neoplasm, one coronary
artery disorder, and one circulatory failure): none
of them was judged to be related to the treatment.
Trivastal L.A., 3 tablets daily, was safe and well tolerated
during 12-month treatment in Parkinsonian patients insufficiently
controlled by L-dopa. |
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A
multicenter trial comparing piribedil (Trivastal
L.A., 3 tablets/day) to bromocriptine (25 mg/day)
in early combination with L-dopa in Parkinson’s
disease |
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| Cesaro
P, Castro-Caldas S, Delwaide P, Jost W, Merello M, Williams
A, et al. Presented at the congress of the European
Federation of the Neurological Society, September 2003,
Helsinki, FIN.
This international study involved 7 countries (United
Kingdom, Germany, France, Portugal, Spain, Belgium,
and Argentina), and 440 patients already established
with L-dopa treatment but insufficiently controlled.
It was a randomized, double-blind study in comparison
with bromocriptine in two parallel groups to assess
Trivastal L.A., 3 tablets daily, in a 12-month treatment.
L-dopa was kept stable until day 42 and then could be
increased afterwards.
The primary end- point was the Unified Parkinson's Disease
Rating Scale motor score (UPDRS III) change versus Day-0
values and the percentage patient responder rates (defined
by a 30% decrease from baseline of UPDRS III score).
The secondary end- points included: a description of
L-dopa daily dose change, UPDRS II score (Activities
of Daily Living), and the clinical global impression
scale (CGI).
At 12 months, Trivastal L.A., 3 tablets daily,
is as effective as bromocriptine in significantly improving
the global motor functioning (UPDRS III score),
offers a positive trend towards the:
- percentage of responders (60.8% vs 58.1%, Δ=2.63),
- lower requirement of L-dopa increase after 1 - year
(7.6 mg vs 16.6 mg, Δ=9),
similarly improve both the patient’s quality of
life (ADL score), and the clinical global impression
(CGI).
Moreover, treatment tolerance and adverse event withdrawals
from Trivastal L.A. group are similar to those in the
bromocriptine group.
The authors conclude that over 12 months, Trivastal
L.A., 3 tablets daily, is as effective as bromocriptine
(25 mg/day) on motor symptoms in parkinsonian patients
insufficiently controlled by L-dopa for a comparable
treatment tolerance and withdrawal rate. |
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| The Parkinson-CONTROL
study |
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The
Parkinson-CONTROL study, a 1-year randomized, double-blind
trial comparing piribedil (150 mg/day) with bromocriptine
(25 mg/day) in early combination with L-dopa in Parkinson’s
disease. |
| Castro-Caldas
A, Cesaro P, Delwaide P, et al. Mov. Disord. 2005. In
press. |
| Abstract
This international study involved 7
countries (United Kingdom, Germany, France, Portugal,
Spain, Belgium, and Argentina), and 440 patients already
established with L-dopa treatment but insufficiently
controlled. It was a randomized, double-blind study
in comparison with bromocriptine in two parallel groups
to assess Trivastal Retard 50, 3 tablets daily, in a
12-month treatment. L-dopa was kept stable until day
42 and then could be increased afterwards.
The primary end- point was the Unified
Parkinson's Disease Rating Scale motor score (UPDRS
III) change versus Day-0 values and the percentage patient
responder rates (defined by a 30% decrease from baseline
of UPDRS III score). The secondary end- points included:
a description of L-dopa daily dose change, UPDRS II
score (Activities of Daily Living), and the clinical
global impression scale (CGI).
At 12 months, Trivastal retard
50, 3 tablets daily,
is as effective as bromocriptine in
significantly improving the global motor functioning
(UPDRS III score),
offers a positive trend towards the:
- percentage of responders (60.8% vs 58.1%, ?=2.63),
- lower requirement of L-dopa increase after 1 - year
(7.6 mg vs 16.6 mg, ?=9),
similarly improve both the patient’s quality of
life (ADL score), and the clinical global impression
(CGI).
Moreover, treatment tolerance and adverse
event withdrawals from Trivastal retard 50 group are
similar to those in the bromocriptine group.
The authors conclude that over 12 months, Trivastal
retard 50, 3 tablets daily, is as effective as bromocriptine
(25 mg/day) on motor symptoms in parkinsonian patients
insufficiently controlled by L-dopa for a comparable
treatment tolerance and withdrawal rate.
Trivastal retard 50 effects
on parkinsonian cognitive dysfunction compared to bromocriptine
in early combination with L-dopa : the Parkinson-CONTROL
study.
Peran P, Cesaro P, Aguilar M, Merello
M, Bodjarian N, Dubois B. Presented at the 8th Congress
of the European Federation of Neurological Societies,
Paris, September 2004. Adapted from European Journal
of Neurology. 2004;11 (suppl 2): 286.
AIM and METHOD
The objective of this study was to
compare Trivastal retard 50 effect (3 tablets/day),
a non-ergot D2/D3 agonist with a2 noradrenergic properties,
to bromocriptine (25 mg/day) on executive functions
and attention.
Patients were parkinsonian patients,
non-demented and non-depressed from an international,
randomized 12-month parallel groups study. Demographic
and disease characteristics (n=178) were similar in
both groups.
RESULTS
After one year of treatment, Trivastal
retard 50 significantly improved the results on the
Wisconsin Card Sorting test. This test measures the
executive functions and the ability for attention. This
improvement of the cognitive status of parkinsonian
patients treated by Trivastal retard 50 [3.2±2.0
– 3.6±1.9] was not found in patients treated
by bromocriptine [4.0±1.9 – 3.7±2.1].
Intragroup analysis demonstrated a significant effect
of Trivastal retard 50 (p=0.035) and no effect of bromocriptine
(p=0.247). Intergroup analysis was in favor of Trivastal
retard 50 (p<0.032). Similar results were found after
6 months, excluding the sole explanation of a re-test
effect.
CONCLUSION
This study gives new proofs of the
beneficial effect of Trivastal retard 50 on the cognitive
status of parkinsonian patients. This improvement of
severe attention impairment linked to the dopamine depletion
could be due to the D2/D3 agonist properties of Trivastal
retard 50. Moreover, it could be related also to the
a2 antagonist properties of Trivastal retard 50 by the
increase of noradrenaline and acetlycholine release
in frontal cortex. |
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A
double blind 2-year extension of the Parkinson-CONTROL
study comparing fixed doses of piribedil (150 mg/day)
and bromocriptine (25 mg/day) in early combination L-dopa
in Parkinson’s disease. |
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| Aguilar
M, Delwaide P, Cesaro G, et al. Presented at the congress
of the Movement Disorder Society, March 2005, New Orleans,
Louisiana, USA. |
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| OBJECTIVE
This is a double-blind 24-month extension of the 12-month
Parkinson-CONTROL study, aimed at assessing the long-term
efficacy of piribedil versus bromocriptine, in early combination
with L-dopa on motor symptoms of PD patients.
|
METHODS
Among the 425 initially randomized
patients, 52 (27 on piribedil and 25 on bromocriptine)
were included in the extended administration period,
continuing in double-blind conditions fixed doses of
piribedil (150 mg/day) plus an adjustable L-dopa daily
dose.
|
RESULTS
A relevant improvement in UPDRS III
was maintained versus baseline over 24 months in both
the piribedil and bromocriptine groups.
Interestingly, the L-dopa daily dose adjustment was
significantly lower in the piribedil group than in the
bromocriptine group.
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CONCLUSION
Early combination of piribedil 150
mg with L-dopa results in relevant improvement of motor
symptoms, L-dopa sparing effect and good sfatey profile
in the long-term treatment of parkinson’s disease.
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Trivastal
retard 50 effects on parkinsonian cognitive dysfunction
compared to bromocriptine in early combination with
L-dopa : the Parkinson-CONTROL study. |
| |
Peran
P, Cesaro P, Aguilar M, Merello M, Bodjarian N, Dubois
B. Presented at the 8th Congress of the European Federation
of Neurological Societies, Paris, September 2004. Adapted
from European Journal of Neurology. 2004;11 (suppl 2):
286. |
| |
AIM
and METHOD
The objective of this study was to compare Trivastal
retard 50 effect (3 tablets/day), a non-ergot D2/D3
agonist with a2 noradrenergic properties, to bromocriptine
(25 mg/day) on executive functions and attention.
Patients were parkinsonian patients, non-demented and
non-depressed from an international, randomized 12-month
parallel groups study. Demographic and disease characteristics
(n=178) were similar in both groups. |
| |
RESULTS
After one year of treatment, Trivastal
retard 50 significantly improved the results on the
Wisconsin Card Sorting test. This test measures the
executive functions and the ability for attention. This
improvement of the cognitive status of parkinsonian
patients treated by Trivastal retard 50 [3.2±2.0
– 3.6±1.9] was not found in patients treated
by bromocriptine [4.0±1.9 – 3.7±2.1].
Intragroup analysis demonstrated a significant effect
of Trivastal retard 50 (p=0.035) and no effect of bromocriptine
(p=0.247). Intergroup analysis was in favor of Trivastal
retard 50 (p<0.032). Similar results were found after
6 months, excluding the sole explanation of a re-test
effect.
|
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CONCLUSION
This study gives new proofs of the
beneficial effect of Trivastal retard 50 on the cognitive
status of parkinsonian patients. This improvement of
severe attention impairment linked to the dopamine depletion
could be due to the D2/D3 agonist properties of Trivastal
retard 50. Moreover, it could be related also to the
a2 antagonist properties of Trivastal retard 50 by the
increase of noradrenaline and acetlycholine release
in frontal cortex. |
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