scholarly journals Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study

CNS Spectrums ◽  
2017 ◽  
Vol 23 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Andrew J. Cutler ◽  
Suresh Durgam ◽  
Yao Wang ◽  
Raffaele Migliore ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Phase Iii ◽  
Open Label ◽  
Two Phase ◽  
Double Blind ◽  
Safety Issues ◽  
Preferential Binding ◽  
Dose Study

ObjectiveCariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia.MethodsThis was a multicenter, open-label, flexible-dose study of cariprazine 3–9 mg/d in adults with schizophrenia. Participants included new patients and patients who had completed one of two phase III lead-in studies (NCT01104766, NCT01104779). Eligible patients entered a no-drug screening period of up to 1 week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment (3–9 mg/d) and 4 weeks of safety follow-up.ResultsA total of 586 patients received open-label cariprazine treatment, ~39% of whom completed the study. No unexpected safety issues or deaths were reported. The most common (≥10%) adverse events (AEs) observed were akathisia (16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and cardiovascular parameters were not considered clinically relevant. Mean body weight increased by 1.5 kg during the study, prolactin levels decreased slightly, and measures of efficacy remained stable.ConclusionsLong-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia.

scholarly journals Oral levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

2019 ◽  
Vol 90 (10) ◽  
pp. 1165-1170 ◽  
Author(s):  
Ammar Al-Chalabi ◽  
Pamela Shaw ◽  
P Nigel Leigh ◽  
Leonard van den Berg ◽  
Orla Hardiman ◽  
...  
Keyword(s):  
Heart Rate ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Lateral Sclerosis

ObjectiveTo evaluate the efficacy and safety of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS). This phase II, randomised, double-blind, placebo-controlled, crossover, three-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60%–90 % of predicted from 11 sites in four countries.MethodsPatients received levosimendan 1 mg daily, 1 mg two times a day or placebo during three 14-day crossover periods and levosimendan 1–2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale-Revised (ALSFRS-R), tolerability and safety.ResultsOf 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being −3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg two times a day (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg two times a day (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events.ConclusionsLevosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase III study to evaluate the longer term effects of oral levosimendan in ALS is ongoing.

scholarly journals Long-Term Efficacy and Safety of Liquid Abobotulinumtoxina Formulation for Moderate-To-Severe Glabellar Lines: A Phase III, Double-Blind, Randomized, Placebo-Controlled and Open-Label Study

2021 ◽  
Author(s):  
Philippe Kestemont ◽  
Said Hilton ◽  
Bill Andriopoulos ◽  
Inna Prygova ◽  
Catherine Thompson ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Neutralizing Antibodies ◽  
Well Being ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Term Efficacy ◽  
Patient Reported

Abstract Background A ready-to-use liquid formulation of abobotulinumtoxinA (aboBoNT-A solution) has been developed. Objectives To assess long-term efficacy and safety of aboBoNT-A solution for glabellar lines (GL) treatment. Methods Multicenter, multinational, Phase III study (NCT02493946), with randomized double-blind placebo-controlled (DBPC; 2:1 aboBoNT-A solution 50 U: placebo) and open-label (OL; 4 cycles aboBoNT-A solution) periods; additional patients were recruited into the OL period. Patients were 18-65 years old; BoNT-naïve; dissatisfied/very dissatisfied with moderate/severe GLs at maximum frown. Investigator’s live assessment (ILA; primary endpoint)/subject’s self-assessment (SSA) of GL severity at maximum frown, patient satisfaction with GL appearance, and FACE-Q patient-reported scales (facial appearance overall, psychological well-being, aging) were assessed. Adverse events (AEs) were monitored. Analyses were performed on DBPC and long-term analysis (LTA; all patients receiving ≥ aboBoNT-A solution injection) populations. Results Mean ages of patients were 46.6–47.8 years, and 89.1–91.3% were female, across DBPC (N=190 [n=126 aboBoNT-A solution, n=64 placebo]) and LTA (N=595) populations. Responder rates for ILA, SSA and patient satisfaction were consistent at Day 29 post-injection across repeat LTA cycles (82.2–87.8%, 62.8–80.6% and 72.2–87.8%, respectively), with statistically significantly higher responder rates versus placebo (DBPC cycle; 81.6% versus 0.8%, 68.1% versus 2.3% and 83.1% versus 5.7%, respectively; all p<0.0001). Consistent improvements on FACE-Q scales occurred with repeat cycles (aboBoNT-A solution versus placebo, p<0.0001 [DBPC cycle]). No new or unexpected AEs, or neutralizing antibodies were observed. Conclusions Results support long-term efficacy and safety of aboBoNT-A solution, and its superiority over placebo, for GL treatment in adults.

Prolonged Overall Survival with Lenalidomide Plus Dexamethasone Compared with Dexamethasone Alone in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 412-412 ◽  
Author(s):  
Donna Weber ◽  
Robert Knight ◽  
Christine Chen ◽  
Andrew Spencer ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prior Treatment ◽  
Phase Iii ◽  
P Value ◽  
Double Blind ◽  
Prior Therapy ◽  
Phase Iii Trials

Abstract Introduction: Lenalidomide (Len), an analog of thalidomide (Thal) is a novel, oral, immunomodulatory agent that is effective against multiple myeloma (MM). In 2 prospective, randomized, double-blind, placebo-controlled phase III trials, Len with dexamethasone (Dex) induced a significantly higher overall response (OR) rate and complete remission (CR) rate, as well as longer time-to-progression (TTP) in comparison with Dex alone. Here, we investigate the long-term overall survival (OS) with Len/Dex. Methods: We evaluated the pooled results from both randomized trials (MM-009, MM-010) of 704 patients who had relapsed or refractory MM, without prior resistance to Dex, who received either Len (25 mg daily for 3 weeks every 4 weeks), or placebo. Dex was given at 40 mg on days 1–4, 9–12, 17–20 every 4 weeks for 4 cycles. From cycle 5 onwards, Dex was given at 40 mg on days 1–4 only. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Follow-up data on OS were obtained up to January 2007. Forty-seven percent of patients who received placebo/Dex crossed over to receive Len +/− Dex. Results: Of 704 patients, 353 were treated with Len/Dex and 351 with Dex alone. Baseline characteristics were well balanced between patients receiving Len/Dex and those receiving Dex alone. Median TTP, OR, and CR were significantly improved in patients treated with Len/Dex compared with Dex alone (Table). Of patients who progressed on Dex alone prior to unblinding, or were found to be receiving Dex alone after unblinding, 47% crossed over to Len +/− Dex. Despite these patients crossing over to Len +/− Dex at progression or at the time of unblinding, the OS was significantly improved in patients treated with Len/Dex compared with Dex alone (hazard ratio 1.295; 95% confidence interval 1.040–1.614; p=0.02). Median OS in the Len/Dex group was 35 months and 31 in the Dex alone group (p<0.05). Median OS was also significantly longer with Len/Dex compared with Dex alone in patients with more than 1 prior therapy (32.4 months versus 27.3 months, p<0.05). Similar median OS was observed with Len/Dex and Dex alone in patients with 1 prior therapy (median OS not yet reached and 35.3 months, p=0.24). Conclusion: With increased follow-up and despite cross-over, patients treated first with Len/Dex had significantly improved OS compared with those treated with Dex alone. Len/Dex (n=353) Dex alone (n=351) P value OR, % 60.6 21.9 <0.001 CR, % 15.0 2.0 <0.001 Median TTP, months 11.2 4.7 <0.001 Median OS, months 35.0 31.0 <0.05 Median OS in patients with 1 prior treatment, months not yet reached 35.3 0.24 Median OS in patients with >1 prior treatment, months 32.4 27.3 <0.05

Can ecstasy treat the agony of PTSD?

2016 ◽  
Vol 33 (S1) ◽  
pp. S10-S10
Author(s):  
M. Mithoefer
Keyword(s):  
Posttraumatic Growth ◽  
Outcome Measures ◽  
Police Officers ◽  
Phase Iii ◽  
High Dose ◽  
Phase Ii Trials ◽  
Open Label ◽  
Double Blind ◽  
Full Dose

IntroductionTwo serotonin reuptake inhibitors (SSRIs) have received FDA indication for treatment of PTSD, however the effectiveness of pharmacotherapy for PTSD is limited. Psychotherapy, including several well established evidence based methods, is the mainstay of PTSD treatment. Despite advances in this area, a significant percentage of PTSD patients are refractory to existing treatments. Recent research has explored the possibility that certain drugs could increase the effectiveness of psychotherapy when administered intermittently in conjunction with psychotherapy sessions. The most robust published. Results to date using this approach have been in early clinical trials of ± 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. These studies primarily involved civilians with treatment-resistant, crime-related PTSD. A more recent phase 2 trial, completed in 2015 yielded equally promising. Results in a cohort of military veterans, police officers and firefighters, mostly veterans from the wars in Iraq and Afghanistan.MethodologyIn these double blind controlled trials subjects with PTSD refractory to prior treatment are randomized to an active dose of MDMA or an active or inactive placebo administered to each individual on only two or three occasions during eight-hour psychotherapy sessions one month apart, in conjunction with preparatory and follow-up psychotherapy sessions. Outcome measures are repeated one or two months after the second MDMA-assisted session before the blind is broken. Subjects who were randomized to full dose MDMA are then eligible for one additional, open label, MDMA-assisted session. Those randomized to placebo or a lower dose of MDMA are eligible for three open-label full dose sessions. Outcome measures are repeated two months following the third MDMA-assisted session. The primary outcome measure is the Clinician Administered PTSD Scale (CAPS). Additional measures include the Beck Depression Inventory-II (BDI-II), Global Assessment of Functioning (GAF), Pittsburgh Sleep Quality Index (PSQI) and Posttraumatic Growth Inventory (PTGI).ResultsIn the original study comparing MDMA with inactive placebo along with the same psychotherapy PTSD was resolved in 83% of the MDMA group vs. 25% of the placebo group receiving the same therapy. Improvement was maintained for at least 74% of subjects at long-term follow-up a mean of 45 months later. In a more recent, unpublished, study both the high dose and the medium dose of MDMA showed large effect sizes in reducing CAPS scores, and improvements in secondary measures: and BDI-II, PSQI, GAF and PTGI.ConclusionEvidence in phase II trials suggest that MDMA-assisted psychotherapy is effective in treating PTSD in both civilians and veterans who have not responded to established treatments. Phase III trials are necessary to definitively establish safety and efficacy of MDMA-assisted psychotherapy for PTSD.Disclosure of interestThe author has not supplied his declaration of competing interest.

scholarly journals Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

2015 ◽  
Vol 21 (10) ◽  
pp. 1322-1331 ◽  
Author(s):  
Andrew D Goodman ◽  
Francois Bethoux ◽  
Theodore R Brown ◽  
Randall T Schapiro ◽  
Ron Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Walking Speed ◽  
Prolonged Release ◽  
Open Label ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Maximum Exposure

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders.

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