T2 Protect AD: Achieving a rapid recruitment timeline in a multisite clinical trial for individuals with mild to moderate Alzheimer's disease.

Introduction: The reporting of approaches facilitating the most efficient and timely recruitment of Alzheimer's disease (AD) patients into pharmacologic trials is fundamental to much-needed therapeutic progress.

Methods: T2 Protect AD (T2), a phase 2 randomized placebo-controlled trial of troriluzole in mild to moderate AD, used multiple recruitment strategies.

Results: T2 exceeded its recruitment target, enrolling 350 participants between July 2018 and December 2019 (randomization rate: 0.

Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial.

Importance: Early identification of Alzheimer disease (AD) is important for clinical management and affords the opportunity to assess potential disease-modifying agents in clinical trials. To our knowledge, this is the first report of a randomized trial to prospectively enrich a study population with prodromal AD (PDAD) defined by cerebrospinal fluid (CSF) biomarker criteria and mild cognitive impairment (MCI) symptoms.

Objectives: To assess the safety of the γ-secretase inhibitor avagacestat in PDAD and to determine whether CSF biomarkers can identify this patient population prior to clinical diagnosis of dementia.

Changes in bone mineral density after 96 weeks of treatment with atazanavir/ritonavir or lopinavir/ritonavir plus tenofovir DF/emtricitabine in treatment-naive patients with HIV-1 infection: the CASTLE body composition substudy.

: Antiretroviral therapy initiation is associated with declines in bone mineral density (BMD), which seem greatest with tenofovir disoproxil fumarate (DF)-containing regimens. Data comparing protease inhibitors are limited. This CASTLE substudy compared paired baseline with week 96 BMD in patients initiating tenofovir DF/emtricitabine plus atazanavir/ritonavir (n = 106) vs lopinavir/ritonavir (n = 70).

Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study.

This study compares the efficacy, safety, and tolerability of a partial dopamine agonist, aripiprazole, with placebo in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. In total, 272 hospitalized patients were randomized to aripiprazole 30 mg/day or placebo in this 3-week, double-blind, placebo-controlled trial. Dosing could be reduced to 15 mg/day for tolerability and, subsequently, increased to 30 mg/day based on clinical response.

Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials.

Aripiprazole is a novel antipsychotic with a unique mechanism of action. Presented here is a pooled analysis of safety and tolerability data from all completed short-term, placebo-controlled trials in schizophrenia from the aripiprazole clinical development program. Data were analyzed from five 4- to 6-week double-blind multicenter studies of patients hospitalized with acute relapse of schizophrenia or schizoaffective disorder randomized to aripiprazole (n=932), placebo (n=416), or haloperidol (n=201).

Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy.

Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder.

Background: Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency: in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep.

Nefazodone and REM sleep: how do antidepressant drugs decrease REM sleep?

In previous uncontrolled studies, nefazodone, a new antidepressant drug, increased REM sleep or had no effect on REM sleep. We report a double-blind, placebo-controlled, parallel group study on effects of nefazodone (N) on polysomnographic sleep variables in healthy human volunteers. Nefazodone was administered for 16 consecutive days, and nocturnal sleep, as well as multiple sleep latency test (MSLT), was monitored before, during, and after N administration.

The safety profile of nefazodone.

Comprehensive review of safety data from approximately 3500 patients who received nefazodone in premarketing clinical trials demonstrates the drug to be very well tolerated, with a favorable side effect profile compared with other antidepressant drugs. Nefazodone treatment was associated with fewer side effects than were the control drugs. The incidence of side effects was generally low, and treatment discontinuations for adverse effects were less frequent with nefazodone than with imipramine and comparable with fluoxetine.

A double-blind comparison of nefazodone, imipramine, and placebo in major depression.

Background: Nefazodone is a 5-HT2-receptor antagonist and serotonin (5-HT) selective reuptake inhibitor. This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder (MDD) in comparison to imipramine and placebo treatments. It also compares two dose ranges of nefazodone to investigate its optimal dose range.