Clinical pharmacology of the dual orexin receptor antagonist ACT-541468 in elderly subjects: Exploration of pharmacokinetics, pharmacodynamics and tolerability following single-dose morning and repeated-dose evening administration

2019 ◽  
Vol 34 (3) ◽  
pp. 326-335 ◽  
Author(s):  
Clemens Muehlan ◽  
Margaux Boehler ◽  
Sander Brooks ◽  
Rob Zuiker ◽  
Joop van Gerven ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Peak Velocity ◽  
Body Sway ◽  
Elderly Subjects ◽  
Maximum Plasma ◽  
Post Dose ◽  
Double Blind ◽  
Pharmacodynamic Effects ◽  
Healthy Elderly ◽  
Evening Administration

Background: The dual orexin receptor antagonist ACT-541468 showed sedative pharmacodynamic effects during initial clinical testing in adult subjects. The present study explored pharmacokinetics, pharmacodynamics and tolerability in healthy elderly subjects. Methods: Double-blind, placebo-controlled, randomised, single-ascending dose study in 24 male/female elderly (65–80 years, 5, 15 and 25 mg in the morning, 6/2 active/placebo per group). Additionally, 10 subjects (8/2 active/placebo) received 25 mg for 7 days in the evening. Pharmacokinetics, pharmacodynamics (saccadic peak velocity, adaptive tracking, body sway, visual analogue scales according to Bowdle and Bond and Lader, Karolinska Sleepiness Scale) and tolerability were assessed. In particular, pharmacodynamics results are to be interpreted exploratorily. Results: Absorption was quick with a median time to maximum concentration of ∼ 1.0 h. The mean elimination half-life was 8.5–9.8 h, the area under the curve and the maximum plasma concentration increased proportionally with dose. Following repeated evening administration of 25 mg, minimal accumulation was observed. There were no pharmacodynamic effects at 5 mg. At 15 mg, saccadic peak velocity (degree/s; SD) was reduced (69; 38), while other variables showed no effects. At 25 mg, effects on all objective pharmacodynamic parameters were observed. At 8–12 h post-dose, there were no differences to placebo and no next-day effects on pharmacodynamic variables after evening administration. Elderly subjects reported fewer adverse events compared to adults in previous studies. Conclusion: ACT-541468 in elderly subjects was well tolerated and pharmacokinetics and pharmacodynamics are compatible with a drug for the treatment of insomnia. Clinicaltrials.gov: NCT02571855

scholarly journals Amino Acid Availability of a Dairy and Vegetable Protein Blend Compared to Single Casein, Whey, Soy, and Pea Proteins: A Double-Blind, Cross-Over Trial

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2613 ◽  
Author(s):  
Jue Liu ◽  
Marianne Klebach ◽  
Monique Visser ◽  
Zandrie Hofman
Keyword(s):  
Amino Acid ◽  
Protein Quality ◽  
Tube Feeding ◽  
Area Under The Curve ◽  
Amino Acid Profile ◽  
Elderly Subjects ◽  
Double Blind ◽  
Healthy Elderly ◽  
Amino Acid Availability ◽  
Pea Proteins

Protein quality is important for patients needing medical nutrition, especially those dependent on tube feeding. A blend of dairy and vegetable proteins (35% whey, 25% casein, 20% soy, 20% pea; P4) developed to obtain a more balanced amino acid profile with higher chemical scores, was compared to its constituent single proteins. Fourteen healthy elderly subjects received P4, whey, casein, soy, and pea (18 g/360 mL bolus) on five separate visits. Blood samples were collected at baseline until 240 min after intake. Amino acid availability was calculated using incremental maximal concentration (iCmax) and area under the curve (iAUC). Availability for P4 as a sum of all amino acids was similar to casein (iCmax and iAUC) and whey (iCmax) and higher vs. soy (iCmax and iAUC) and pea (iCmax). Individual amino acid availability (iCmax and iAUC) showed different profiles reflecting the composition of the protein sources: availability of leucine and methionine was higher for P4 vs. soy and pea; availability of arginine was higher for P4 vs. casein and whey. Conclusions: The P4 amino acid profile was reflected in post-prandial plasma levels and may be regarded as more balanced compared to the constituent single proteins.

Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly

2002 ◽  
Vol 33 (1) ◽  
pp. 41-49 ◽  
Author(s):  
R. J. PORTER ◽  
B. S. LUNN ◽  
J. T. O'BRIEN
Keyword(s):  
Cognitive Function ◽  
Rating Scales ◽  
Senile Dementia ◽  
Specific Effect ◽  
Acute Tryptophan Depletion ◽  
Elderly Subjects ◽  
Tryptophan Depletion ◽  
Emotional Symptoms ◽  
Double Blind ◽  
Healthy Elderly

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

scholarly journals Residual effects of eszopiclone and placebo in healthy elderly subjects: a randomized double-blind study

2017 ◽  
Vol 15 (3) ◽  
pp. 235-241 ◽  
Author(s):  
Jun Takahashi ◽  
Takashi Kanbayashi ◽  
Sachiko Ito Uemura ◽  
Youhei Sagawa ◽  
Kou Tsutsui ◽  
...  
Keyword(s):  
Blind Study ◽  
Residual Effects ◽  
Elderly Subjects ◽  
Double Blind Study ◽  
Double Blind ◽  
Healthy Elderly ◽  
Healthy Elderly Subjects

Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects

2021 ◽  
Author(s):  
Jack Ansell ◽  
Sasha Bakhru ◽  
Bryan E Laulicht ◽  
Gregory Tracey ◽  
Stephen Villano ◽  
...  
Keyword(s):  
Steady State ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hot Flashes ◽  
Elderly Subjects ◽  
Reversal Agent ◽  
Post Dose ◽  
Healthy Elderly ◽  
Complete Reversal

Abstract Aims  Ciraparantag is a reversal agent for anticoagulants including direct oral anticoagulants. The aim was to evaluate the efficacy and safety of ciraparantag to reverse anticoagulation induced by apixaban or rivaroxaban in healthy elderly adults. Methods and results  Two randomized, placebo-controlled, dose-ranging trials conducted in healthy subjects aged 50–75 years. Subjects received apixaban (Study 1) 10 mg orally twice daily for 3.5 days or rivaroxaban (Study 2) 20 mg orally once daily for 3 days. At steady-state anticoagulation subjects were randomized 3:1 to a single intravenous dose of ciraparantag (Study 1: 30, 60, or 120 mg; Study 2: 30, 60, 120, or 180 mg) or placebo. Efficacy was based on correction of the whole blood clotting time (WBCT) at multiple timepoints over 24 h. Subjects and technicians performing WBCT testing were blinded to treatment. Complete reversal of WBCT within 1 h post-dose and sustained through 5 h (apixaban) or 6 h (rivaroxaban) was dose related and observed with apixaban in 67%, 100%, 100%, and 17% of subjects receiving ciraparantag 30 mg, 60 mg, 120 mg, or placebo, respectively; and with rivaroxaban in 58%, 75%, 67%, 100%, and 13% of subjects receiving ciraparantag 30 mg, 60 mg, 120 mg, 180 mg, or placebo, respectively. Adverse events related to ciraparantag were mild, transient hot flashes or flushing. Conclusions  Ciraparantag provides a dose-related reversal of anticoagulation induced by steady-state dosing of apixaban or rivaroxaban. Sustained reversal was achieved with 60 mg ciraparantag for apixaban and 180 mg ciraparantag for rivaroxaban. All doses of ciraparantag were well tolerated.

scholarly journals 0358 RESIDUAL EFFECTS OF ESZOPICLONE AND PLACEBO IN HEALTHY ELDERLY SUBJECTS, A RANDOMIZED DOUBLE BLIND STUDY

SLEEP ◽  
2017 ◽  
Vol 40 (suppl_1) ◽  
pp. A133-A133
Author(s):  
J Takahahsi ◽  
K Takashi ◽  
S Ito Uemura ◽  
Y Sagawa ◽  
K Tsutsui ◽  
...  
Keyword(s):  
Blind Study ◽  
Residual Effects ◽  
Elderly Subjects ◽  
Double Blind Study ◽  
Double Blind ◽  
Healthy Elderly ◽  
Healthy Elderly Subjects

scholarly journals Influence of a combination ofLactobacillus acidophilusNCFM and lactitol on healthy elderly: intestinal and immune parameters

2008 ◽  
Vol 101 (3) ◽  
pp. 367-375 ◽  
Author(s):  
Arthur C. Ouwehand ◽  
Kirsti Tiihonen ◽  
Markku Saarinen ◽  
Heli Putaala ◽  
Nina Rautonen
Keyword(s):  
Intestinal Microbiota ◽  
Bowel Function ◽  
Elderly Subjects ◽  
Immune Markers ◽  
Double Blind ◽  
Healthy Elderly ◽  
Immune Parameters ◽  
Age Related ◽  
Over Time ◽  
Healthy Elderly Subjects

With increasing age, a number of physiological changes take place which are reflected in immune and bowel function. These changes may relate to the commonly assumed age-related changes in intestinal microbiota; most noticeably a reduction in bifidobacteria. The current study aimed at modifying the intestinal microbiota with a potential synbiotic on selected immune and microbiota markers. Healthy elderly subjects were randomised to consume during 2 weeks either a placebo (sucrose) or a combination of lactitol andLactobacillus acidophilusNCFM twice daily in a double-blind parallel trial. After the intervention, stool frequency was higher in the synbiotic group than in the placebo group and a significant increase in faecalL. acidophilusNCFM levels was observed in the synbiotic group, after baseline correction. In contrast to the generally held opinion, the study subjects had faecalBifidobacteriumlevels that were similar to those reported in healthy young adults. These levels were, nevertheless, significantly increased by the intervention. Levels of SCFA were not changed significantly. Of the measured immune markers, PGE2levels were different between treatments and IgA levels changed over time. These changes were modest which may relate to the fact that the volunteers were healthy. Spermidine levels changed over time which may suggest an improved mucosal integrity and intestinal motility. The results suggest that consumption of lactitol combined withL. acidophilusNCFM twice daily may improve some markers of the intestinal microbiota composition and mucosal functions.

scholarly journals Comparative study of the effects of two programs of physical exercises in flexibility and balance of healthy elderly individuals with and without major depression

2011 ◽  
Vol 9 (3) ◽  
pp. 307-312 ◽  
Author(s):  
Fernanda Varkala Lanuez ◽  
Wilson Jacob-Filho ◽  
Mariana Varkala Lanuez ◽  
Ana Cláudia Becattini de Oliveira
Keyword(s):  
Major Depression ◽  
The Elderly ◽  
Controlled Study ◽  
Elderly Subjects ◽  
Research Subjects ◽  
Double Blind ◽  
Elderly Individuals ◽  
Healthy Elderly ◽  
Physical Exercises ◽  
Balance Exercises

ABSTRACT Objective: To assess flexibility and balance in healthy elderly subjects with or without major depression, by means of two different programs: aerobic exercises and flexibility and balance exercises. Methods: A randomized, double-blind controlled study in which each sample was the control of itself. Research subjects were 19 healthy elderly individuals, aged between 60 and 90 years, of both genders, referred to the Department of Geriatrics of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, with or without the diagnosis of major depression, and sedentary or that had not engaged in physical activity for at least 6 months. Results: Subjects with major depression, as well as those without depression, showed signifcant improvement in flexibility and balance, especially in the group that did aerobic exercises. Conclusion: The results of this investigation reinforce the relevance of physical exercises for the elderly with major depression, as this is an important tool for treating and following-up this group of patients.

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