Safety of Rimegepant in Adults with Migraine and Anxiety, Depression, or Using Antidepressants: Analysis of a Multicenter, Long-Term, Open-Label Study.

Introduction: Anxiety and depression are frequently associated with migraine, and antidepressant use can complicate treatment. These analyses assessed the safety and tolerability of rimegepant in participants with migraine and anxiety and/or depression, or using selective serotonin reuptake inhibitors (SSRIs) and/or other antidepressants.

Methods: Data were from a phase II/III safety study of rimegepant for the acute treatment of migraine.

Long-Term Use of Rimegepant 75 mg for the Acute Treatment of Migraine is Associated with a Reduction in the Utilization of Select Analgesics and Antiemetics.

Purpose: To examine use of concomitant analgesics and antiemetics during treatment with rimegepant in adults with migraine.

Patients And Methods: This was a post hoc analysis of a long-term, open-label, safety study in adults with a history of 2-14 moderate or severe migraine attacks per month. Participants self-administered rimegepant 75 mg (1) up to once daily as needed (PRN) for 52 weeks or (2) every other day plus PRN (EOD+PRN) for 12 weeks.

Investigating CNS distribution of PF-05212377, a P-glycoprotein substrate, by translation of 5-HT receptor occupancy from non-human primates to humans.

PF-05212377 (SAM760) is a potent and selective 5-HT antagonist, previously under development for the treatment of Alzheimer's disease. In vitro, PF-05212377 was determined to be a P-gp/non-BCRP human transporter substrate. Species differences were observed in the in vivo brain penetration of PF-05212377 with a ratio of the unbound concentration in brain/unbound concentration in plasma (C /C ) of 0.

Pharmacokinetic and Pharmacodynamic Effects of a γ-Secretase Modulator, PF-06648671, on CSF Amyloid-β Peptides in Randomized Phase I Studies.

γ-Secretase modulators (GSMs) represent a promising therapy for Alzheimer's disease by reducing pathogenic amyloid-β (Aβ) peptide production. Three phase I studies (NCT02316756, NCT02407353, and NCT02440100) investigated the safety/tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the oral GSM, PF-06648671. A PK/PD indirect-response model was developed (using biomarker data) to simultaneously characterize differential effects of PF-06648671 on multiple Aβ species in cerebrospinal fluid (CSF).

A Phase 2 clinical trial of PF-05212377 (SAM-760) in subjects with mild to moderate Alzheimer's disease with existing neuropsychiatric symptoms on a stable daily dose of donepezil.

Background: Symptomatic benefits have been reported for 5-HT receptor antagonists in Alzheimer's disease (AD) trials. SAM-760 is a potent and selective 5-HT receptor antagonist that has demonstrated central 5-HT receptor saturation in humans at a dose of 30 mg.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial evaluating the efficacy and safety of SAM-760 30 mg once daily (QD) for 12 weeks in subjects with AD on a stable regimen of donepezil 5 to 10 mg QD.

Disease progression model for cognitive deterioration from Alzheimer's Disease Neuroimaging Initiative database.

Background: A mathematical model was developed to describe the longitudinal response in Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) obtained from the Alzheimer's Disease Neuroimaging Initiative.

Methods: The model was fit to the longitudinal ADAS-cog scores from 817 patients. Risk factors (age, apolipoprotein ɛ4 [APOE ɛ4] genotype, gender, family history of AD, years of education) and baseline severity were tested as covariates.

Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers.

This study was designed to investigate the multiple-dose pharmacokinetics, safety, and tolerability of the selective α4β2 nicotinic acetylcholine partial agonist, varenicline, in elderly (65-85 years old) nonsmokers. Fifty male and female subjects with normal renal function for their age were randomized to receive varenicline or placebo once or twice daily for 3 weeks in an investigator- and subject-blinded parallel-group design. Treatment regimens included weekly titration (n = 14; days 1-7, 0.

Disease progression meta-analysis model in Alzheimer's disease.

Background: Various authors have evaluated disease progression in Alzheimer's disease (AD), using patient data from individual clinical studies or pooled data across various trials. We conducted a systematic review of public data sources from 1990 to 2008 for all available AChE inhibitor studies, as well as clinical studies that evaluated the rate of deterioration in AD patients. Unique to this analysis, we developed a model based on literature data to describe the longitudinal response in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog) (change from baseline) in mild to moderate severity AD patients.

Pharmacokinetics, safety, and tolerability after single and multiple oral doses of varenicline in elderly smokers.

Varenicline is a novel selective alpha4beta2 nicotinic acetylcholine partial agonist developed for smoking cessation. This study investigated the single- and multiple-dose pharmacokinetics, safety, and tolerability of varenicline in elderly (> or = 65 years) smokers. Twenty-four elderly smokers with normal renal function for their age (estimated creatinine clearance > or = 70 mL/min) received varenicline 1 mg once daily (n = 8) or placebo (n = 4) for 7 days, or 1 mg twice daily (n = 8) or placebo (n = 4) for 6 days with a single dose on day 7 in a double-blind, parallel group and placebo-controlled design.