Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease

Neurology ◽  
2018 ◽  
Vol 90 (21) ◽  
pp. e1849-e1857 ◽  
Author(s):  
Joaquim J. Ferreira ◽  
Andrew J. Lees ◽  
Werner Poewe ◽  
Olivier Rascol ◽  
José-Francisco Rocha ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Double Blind Study ◽  
Class Iii ◽  
Open Label ◽  
Double Blind ◽  
Dopaminergic Therapy ◽  
One Year ◽  
Off Time

ObjectiveTo evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease.MethodsAfter completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments. The primary efficacy variable was the change from baseline in absolute “off” time based on patient diaries. Other outcomes included proportion of responders, scale-based assessments, and standard safety assessments.ResultsOne year of treatment with opicapone reduced “off” time by a half-hour (33.8 minutes) vs the open-label baseline and >2 hours (126.9 minutes) vs the double-blind baseline. Whereas patients who were originally treated with opicapone 50 mg in the double-blind phase maintained their efficacy, switching treatments led to further decreases in “off” time (−64.9, −39.3, −27.5, and −23.0 minutes for switching from placebo, entacapone, and opicapone 5 and 25 mg, respectively). Dyskinesia was the most frequently reported adverse event (14.5%) and was managed by adjustment of dopaminergic therapy. No new safety concerns were observed with long-term opicapone administration.ConclusionLong-term use of opicapone provided sustained efficacy over 1 year. Switching from entacapone to opicapone led to enhanced efficacy under the conditions of the study.Classification of evidenceThis study provides Class III evidence that for patients with Parkinson disease and end-of-dose motor fluctuations, long-term use (52 weeks) of opicapone is well tolerated and reduces “off” time.

The long-term effects of homeopathic treatment of chronic headaches: one year follow-up and single case time series analysis

2001 ◽  
Vol 90 (02) ◽  
pp. 63-72 ◽  
Author(s):  
H Walach ◽  
T Lowes ◽  
D Mussbach ◽  
U Schamell ◽  
W Springer ◽  
...  
Keyword(s):  
Time Series ◽  
Single Case ◽  
Double Blind Study ◽  
Long Term Effects ◽  
Double Blind ◽  
Homeopathic Treatment ◽  
Chronic Headaches ◽  
One Year

AbstractLittle is known about long-term effects of homeopathic treatment. Following a double-blind, placebo controlled trial of classical homeopathy in chronic headaches, we conducted a 1-year observational study of 18 patients following the double-blind phase, and a complete follow-up study of all trial participants. Eighteen patients received free treatment for daily diary data (frequency, intensity, duration of headaches) over the course of 1 y. All patients enrolled in the double-blind study were sent a 6-week headache diary, a follow-up questionnaire, a personality inventory and a complaint list. Eighty-seven, of the original 98 patients enrolled returned questionnaires, 81 returned diaries. There was no additional change from the end of the trial to the one-year follow-up. The improvement seen at the end of the 12-week trial was stable after 1 y. No differential effects according to treatment after the trial could be seen. Patients with no treatment following the trial had the most improvement after 1 y. Five of 18 patients can be counted responders according to ARIMA analysis of single-case time-series. Patients with double diagnoses and longer treatment duration tended to have clearer improvements than the rest of the patients. Approximately 30% of patients in homeopathic treatment will benefit after 1 y of treatment. There is no indication of a specific, or of a delayed effect of homeopathy.

Long-term (LT) disease control in patients (pts) with hormone receptor-positive (HR+), PIK3CA-altered advanced breast cancer (ABC) treated with alpelisib (ALP) + fulvestrant (FUL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1054-1054
Author(s):  
Dejan Juric ◽  
Fabrice Andre ◽  
Udaiveer Panwar ◽  
Filip Janku ◽  
Yen-Shen Lu ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase 1 ◽  
Estrogen Therapy ◽  
Dose Intensity ◽  
Double Blind Study ◽  
Open Label ◽  
Double Blind ◽  
Pik3ca Mutations ◽  
Grade 3

1054 Background: PIK3CA mutations, present in ̃40% of HR+, HER2– ABC, are associated with therapeutic resistance and shorter survival. Alpelisib (ALP) + fulvestrant (FUL) demonstrated efficacy in this population for which achieving long-term (LT) disease control is challenging. Here, we report on pts with HR+, PIK3CA-altered ABC who achieved LT disease control with ALP + FUL. Methods: SOLAR-1 was a phase 3, randomized, double-blind study of ALP (or placebo) + FUL in HR+, HER2– ABC that progressed on/after an aromatase inhibitor. CBYL719X2101 (X2101) was a phase 1, open-label study of escalating ALP doses ± FUL in advanced solid tumors that progressed on/after anti-estrogen therapy (ET) or relapsed after adjuvant anti-ET. A cut-off ≥ median (progression-free survival [PFS] + 2 SE) was chosen based on Kaplan-Meier curves from SOLAR-1 to define LT disease control as PFS (SOLAR-1) or time on treatment (X2101) ≥18 mo. Results: In SOLAR-1, 51 of 169 pts (30.2%) randomized to ALP + FUL achieved LT disease control with a median PFS of 33.5 mo (95% CI, 27.4 mo-not reached). Baseline characteristics of pts in SOLAR-1 are in the table below. In pts with LT disease control, adverse events (AEs) of special interest (combined preferred terms) of GI toxicity were observed in 47 pts (92.2%; grade ≥3: 11.8%, n=6), of hyperglycemia in 41 pts (80.4%; grade ≥3: 39.2%, n=20), and of rash in 28 pts (54.9%; grade ≥3: 19.6%, n=10). Median ALP relative dose intensity was 79.9% and 82.1% for pts with LT disease control (n=51) and the overall population (n=168), respectively. In X2101, 7 of 52 pts (13.5%) with ABC who received ALP+FUL achieved LT disease control up to 47.8 mo. Conclusions: In this subset of pts with hard-to-treat, endocrine-resistant disease, LT disease control ≥18 mo is meaningful considering median PFS of 4.6-9.3 mo or 9.5-16.4 mo with FUL alone or with cyclin-dependent kinase 4/6 inhibitors, respectively. Here, LT disease control was observed in 2 studies of HR+, PIK3CA-altered ABC, including in pts with poor prognosis, diabetes/pre-diabetes at baseline, and heavy pre-treatment. AE profile was consistent with prior reports and did not preclude LT disease control. Further work is needed to better understand factors influencing LT disease control. Clinical trial information: NCT01219699, NCT02437318 .[Table: see text]

scholarly journals 100 Olanzapine/Samidorphan for Schizophrenia: Weight Gain and Metabolic Outcomes in Phase 3 ENLIGHTEN-2 and Subsequent Long-Term, Open-Label Safety Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 265-265
Author(s):  
Christoph U. Correll ◽  
John W. Newcomer ◽  
Bernard Silverman ◽  
Lauren DiPetrillo ◽  
Christine Graham ◽  
...  
Keyword(s):  
Weight Gain ◽  
Waist Circumference ◽  
Metabolic Parameters ◽  
Opioid Antagonist ◽  
Metabolic Parameter ◽  
Double Blind Study ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind

Abstract:Background:Opioid antagonists may mitigate medication-associated weight gain and/or metabolic dysregulation. ENLIGHTEN-2 evaluated a combination of olanzapine and the opioid antagonist samidorphan (OLZ/SAM) vs olanzapine for effects on weight gain and metabolic parameters over 24 weeks in adults with stable schizophrenia.METHODS:This phase 3, double-blind study (ClinicalTrials.gov: NCT02694328) enrolled adults 18–55 yo with stable schizophrenia, randomized 1:1 to once-daily OLZ/SAM or olanzapine. Co-primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. Waist circumference and fasting metabolic parameters were also measured. Completers could enter a 52-week open-label safety extension.RESULTS:561 patients were randomized: 550 were dosed, 538 had ≥1 post-baseline weight assessment, and 352 (64%) completed; 10.9% discontinued due to AEs. At week 24, least squares mean (SE) percent weight change from baseline was 4.21 (0.68)% with OLZ/SAM and 6.59 (0.67)% with olanzapine (difference, −2.38 [0.76]%; P=0.003). Fewer patients treated with OLZ/SAM (17.8%) had ≥10% weight gain vs olanzapine (29.8%; odds ratio=0.50; P=0.003). The change from baseline in waist circumference was significantly smaller with OLZ/SAM (P<0.001). Common AEs (≥10%) with OLZ/SAM and olanzapine were weight increased (24.8%, 36.2%), somnolence (21.2%, 18.1%), dry mouth (12.8%, 8.0%), and increased appetite (10.9%, 12.3%), respectively. Metabolic parameter changes were generally small and remained stable with long-term OLZ/SAM treatment.DISCUSSION:OLZ/SAM treatment limited weight gain associated with olanzapine. Metabolic parameter changes were generally small, similar between groups over 24 weeks, and remained stable over an additional 52 weeks of open-label OLZ/SAM treatment.Funding Acknowledgements:This study was funded by Alkermes, Inc.

scholarly journals Long-term safety and efficacy of opicapone in Japanese Parkinson’s patients with motor fluctuations

2021 ◽  
Author(s):  
Atsushi Takeda ◽  
Ryosuke Takahashi ◽  
Yoshio Tsuboi ◽  
Masahiro Nomoto ◽  
Tetsuya Maeda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Motor Fluctuations ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Off Time

AbstractThe double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson’s Disease) study in Japanese levodopa-treated patients with Parkinson’s disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [− 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [− 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [− 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.

scholarly journals Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension

Cephalalgia ◽  
2020 ◽  
pp. 033310242097399
Author(s):  
Richard B Lipton ◽  
Stewart J Tepper ◽  
Stephen D Silberstein ◽  
David Kudrow ◽  
Messoud Ashina ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Chronic Migraine ◽  
Controlled Trial ◽  
Treatment Phase ◽  
Episodic Migraine ◽  
Double Blind Study ◽  
Open Label ◽  
Double Blind ◽  
Clinical Trial Registration

Objective To determine reversion rates from chronic migraine to episodic migraine during long-term erenumab treatment. Methods A daily headache diary was completed during the 12-week, double-blind treatment phase of a placebo-controlled trial comparing erenumab 70 mg, 140 mg, and placebo, and weeks 1–12, 21–24, 37–40, and 49–52 of the open-label treatment phase. Chronic migraine to episodic migraine reversion rates were assessed over the double-blind treatment phase; persistent reversion to episodic migraine over 24 weeks (double-blind treatment phase through the first 12 weeks in the open-label treatment phase), long-term persistent reversion to episodic migraine over 64 weeks (double-blind treatment phase plus open-label treatment phase); delayed reversion to episodic migraine through the first 12 weeks of the open-label treatment phase among patients remaining in chronic migraine during the double-blind treatment phase. Results In the double-blind treatment phase, 53.1% (95% confidence interval: 47.8–58.3) of 358 erenumab-treated completers had reversion to episodic migraine; monthly reversion rates to episodic migraine were typically higher among patients receiving 140 mg versus 70 mg. Among 181 completers (receiving erenumab for 64 weeks), 98 (54.1% [95% confidence interval: 46.6–61.6]) had reversion to episodic migraine during the double-blind treatment phase; of those, 96.9% (95% confidence interval: 91.3–99.4) had persistent reversion to episodic migraine, 96.8% (95% confidence interval: 91.1–99.3) of whom had long-term persistent reversion to episodic migraine. Delayed reversion to episodic migraine occurred in 36/83 (43.4% [95% confidence interval: 32.5–54.7]) patients; of these, 77.8% (95% confidence interval: 60.9–89.9) persisted in reversion through week 64. Conclusions Patients with reversion to episodic migraine at week 12 will likely persist as episodic migraine with longer-term erenumab; others may achieve delayed reversion to episodic migraine. Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02066415

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