None listed
Conditions
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 dementia. RIV is available in two forms, oral (capsule) 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 nasally (into the nose) provides RIV therapeutic levels in the blood plasma that are comparable to Exelon (Registered Trademark) oral capsule and whether nasal RIV results in lower side effects. 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 a phase 1 trial in 16 young healthy males aged 18 to 55 years. While comparing the two delivery methods, this study will also investigate the safety and tolerability of Rivastigmine nasal spray.
Interventions
Treatment A: Rivastigmine Nasal Spray 4mg as single dose (One spray each nostril)
Treatment B: Exelon (Registered Trademark) 3mg oral capsule as single dose
Participants randomised to receive each treatment as a crossover with a single dose given on the first day, followed by a 2-day washout and a single dose given on the fourth day. Treatments administered by site staff to participants under direct supervision.
Sponsors
Lachesis Biosciences Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
- Healthy males between 18 and 55 years (inclusive) of age. - No known history of clinically significant liver, neurological, renal, cardiovascular, respiratory (asthma), endocrinological, gastrointestinal, haematopoietic disease, neoplasm or any other clinically significant medical disorder, which in the 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 rivastigmine, components (benzyl alcohol, benzoates), other carbamates or ondansetron. - Current symptomatic allergic rhinitis. - Presence of significant disease or anatomical abnormality affecting the nasal passages. - History of or currently active asthma or chronic obstructive pulmonary disease, excluding childhood asthma. - Use of any prescription, OTC or herbal medication within 7 days or 5 half-lives (whichever is longer) of study drug administration, with the exception of the oral contraceptive pill, paracetamol up to 2g daily and low-moderate dose NSAID. - History of or currently active cardiac arrhythmias such as bradycardia and sick sinus syndrome. - History of heart block or disease of cardiac conducting system. - 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 aetiology.
Outcome results
None listed