Clinical trial NCT02291783: Phase I, Healthy Subject, Safety, Tolerability and Pharmacokinetic Study of an M1 Agonist to Treat Cognitive Impairment
Official title: A Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of HTL0009936 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Nxera Pharma UK Limited
Sponsor class: INDUSTRY
First posted: 2014-11-14
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders.

Detailed description: The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders. This study is a single ascending dose study.

Eligibility criteria: Inclusion Criteria:

* Body mass index of ≥19 and ≤ 30kg/m²
* Healthy subject free from any clinically significant illness or disease
* Female subjects must be ≥65 years

Exclusion Criteria:

* Subject who is predicted to be a CYP2D6 poor or ultra rapid metabolizer
* History of hypersensitivity to study drug
* History of epilepsy or seizures
* Subject with previous history of suicidal behavior
* Subjects with significant hearing impairment
* Subjects with an abnormal EEG

Primary outcomes:
measure: Number of participants with Adverse Events, as a measure of safety and tolerability
timeFrame: From signing of informed consent up to 30 days after the final visit
measure: Changes in Safety Lab parameters as a measure of safety and tolerability
timeFrame: Screening, Day-1, at select dosing days, and at 5 to 7 days post dose for single doseand 15 to 17 days post first dose in multiple dosing.
measure: Changes in vital signs as a measure of safety and tolerability
timeFrame: Screening, Day-1, at select dosing days and at 5 to 7 days post dose for single dose, and 15 to 17 days post first dose in multiple dosing.
measure: Changes in 12-lead electrocardiograms as a measure of safety and tolerability
timeFrame: Screening, pre-dose, at select dosing days and at 5 to 7 days post dose for single dose,and 15 to 17 days post first dose in multiple dosing.
Secondary outcomes:
measure: Pharmacokinetic measures in plasma as measured by Peak plasma concentration (Cmax)
timeFrame: Pre-dose, multiple time points to 24h, at select dosing days, and 5 to 7 days post dosefor single dose,and 15 to 17 days post first dose in multiple dosing.
measure: Pharmacokinetic measures in cerebro spinal fluid (CSF) in young males as measured by max observed CSF (Cmax CSF)
timeFrame: Part 1 - 1h, 2h,3h post dose
measure: Pharmacokinetic measures to assess the food effect as measured by ANOVA
timeFrame: Pre-dose, multiple time points to 24h, and at 12h, 24h and 5 to 7 days post dose.
measure: Pharmacodynamic response as measured by pupillometry
timeFrame: Multiple time points Day1 to 6h post dose Part 1 only.
measure: Pharmacokinetic measures in urine in young males and elderly male and female subjects as measured by amount of urine excreted at collection intervals
timeFrame: Pre-dose,multiple 4h collection intervals to 24h post dose on select dosing days to Day 10 for multiple dosing.
measure: Pharmacodynamic response as measured by Bond and Lader visual analogue scale
timeFrame: Day 1 at multiple timepoints to 24h post dose.
measure: Pharmacodynamic response as measured by changes in qEEG and Event Related Potentials (ERP)
timeFrame: Screening, Day-1, Day 4, Day 9 multiple dosing regimen only
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Parexel Early Phase Clinical Unit
state: Middlesex
Study officials:
affiliation: Parexel
name: Annelize Koch, MBChB
role: PRINCIPAL_INVESTIGATOR
References: