Evaluation of the Pharmacokinetics and Safety of Rivastigmine Intranasal Spray

A Sequential, Crossover, Pharmacokinetic and Safety Study of Single Dose Rivastigmine Intranasal Spray (3.126mg) and Single Dose Intravenous Solution (1mg) to Evaluate the Absolute Bioavailability of Rivastigmine Intranasal Spray in Healthy Elderly Volunteers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12614001313628

Enrollment

Registered

2014-12-16

Start date

2015-03-10

Completion date

2015-03-20

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Rivastigmine (RIV) is an acetylcholine esterase inhibitor which prevents neurotransmitter breakdown. As such it is currently approved for the treatment of neurological disorders such as Alzheimer's and Parkinson's disease. RIV is available in two forms, oral (capsule and liquid) and as a transdermal (through the skin) patch. The latter was developed as a consequence of the oral forms causing nausea, vomiting and diarrhoea predominantly caused by the low oral bioavailability of this drug. Although the transdermal patch overcomes a lot of these side effects, a high percentage of people suffer from skin irritation and possible sleeplessness. This study will investigate whether delivering RIV intranasally (into the nose), results in lower side effects, while maintaining the desired therapeutic effect. As such this study will compare the bioavailability of intranasal delivery to intravenous delivery of RIV at a level that is reported to be therapeutically beneficial. Each intervention will be as a single dose with thorough blood sampling over 24 hours to assess drug levels; each intervention will be separated by a 2 day washout period. This is an exploratory phase 1 trial in 8 healthy elderly males and females aged 55 to 85 years. While comparing the two delivery methods, this study will also investigate the safety and tolerability of intranasal Rivastigmine.

Interventions

Arm 1: First day, Intravenous Rivastigmine 1mg (delivered by infusion pump over 30 minutes) followed by a 2-day washout Arm 2: Fourth day, Rivastigmine Intranasal Spray 3.126mg as single dose (One spray each nostril)

Study design

Allocation

Non-randomised trial

Intervention model

Crossover

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

55 Years to 85 Years

Healthy volunteers

Yes

Inclusion criteria

- Healthy Caucasian males and females between 55 and 85 years (inclusive) of age. - No known history of clinically significant neurological, renal, cardiovascular, respiratory (asthma), endocrinological, gastrointestinal, haematopoietic disease, neoplasm or any other clinically significant medical disorder, which in the Principal Investigator's judgment contraindicate administration of the study interventions. - BMI 18-32 (inclusive) calculated as Weight (Kg)/Height (sq.m).

Exclusion criteria

- Known hypersensitivity to the drug, components (benzyl alcohol, benzoates) or other carbamates. - Current symptomatic allergic rhinitis - History of or currently active asthma or chronic obstructive pulmonary disease, excluding childhood asthma. - History of or currently active cardiac arrhythmias such as bradycardia and sick sinus syndrome. - History of urinary tract obstruction. - History of or currently active GI diseases such as peptic ulcer, GERD, bleeding or history of any GI surgery other than appendectomy or herniotomy, or with any gastrointestinal disorder likely to influence drug absorption, or with any history of anorexia, frequent nausea or emesis, regardless of etiology. - Use of any beta-blocker class prescription drug, cholinomimetic and anticholinergic drugs, including atropine, tricyclic antidepressants and anti-histamines.

Outcome results