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Completed

NCT Number: NCT02291783

Phase I, Healthy Subject, Safety, Tolerability and Pharmacokinetic Study of an M1 Agonist to Treat Cognitive Impairment

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.

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Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Parexel Early Phase Clinical Unit

Harrow, Middlesex, HA1 3UJ, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

HTL0009936

Drug

Single dose

Other names: 9936, HTL0009936

HTL0009936 placebo

Drug

Placebo single dose

Other names: Placebo

Primary outcomes

  1. Number of participants with Adverse Events, as a measure of safety and tolerability

    Time frame: From signing of informed consent up to 30 days after the final visit

    AE reports include a description of the AE, date and time of onset and resolution, intensity, and relationship to IMP.

  2. Changes in Safety Lab parameters as a measure of safety and tolerability

    Time frame: 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.

    Hematology, clinical chemistry, urinalysis

  3. Changes in vital signs as a measure of safety and tolerability

    Time frame: 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.

    Pulse rate,body temperature,blood pressure, and orthostatic changes.

  4. Changes in 12-lead electrocardiograms as a measure of safety and tolerability

    Time frame: 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.

    Change in ECG parameters

Secondary outcomes

  1. Pharmacokinetic measures in plasma as measured by Peak plasma concentration (Cmax)

    Time frame: 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.

    Peak plasma concentration (Cmax), time at occurrence of Cmax (tmax), Area under the plasma concentration versus time curve (AUC) 0-t, 0- infinity, percent of AUC 0-infinity, Cmax normalized by dose, AUC 0-t normalized for dose.

  2. Pharmacokinetic measures in cerebro spinal fluid (CSF) in young males as measured by max observed CSF (Cmax CSF)

    Time frame: Part 1 - 1h, 2h,3h post dose

    Maximum observed CSF concentration (Cmax CSF), area under the CSF concentration versus time

  3. Pharmacokinetic measures to assess the food effect as measured by ANOVA

    Time frame: Pre-dose, multiple time points to 24h, and at 12h, 24h and 5 to 7 days post dose.

    Food effect analysis will be based on analysis of variance (ANOVA) for treatment differences.

  4. Pharmacodynamic response as measured by pupillometry

    Time frame: Multiple time points Day1 to 6h post dose Part 1 only.

    Changes in average pupil diameter as measured in 3 different conditions of lux.

  5. Pharmacokinetic measures in urine in young males and elderly male and female subjects as measured by amount of urine excreted at collection intervals

    Time frame: Pre-dose,multiple 4h collection intervals to 24h post dose on select dosing days to Day 10 for multiple dosing.

    Amount excreted in urine at each collection interval (Ae1-t2) all parts. Cumulative amount excreted to 12h and 24h (Ae0-t) depending on Part. Cumulative urine excreted of unchanged drug to 24h (Fe%) and to 12h depending on Part. Volume of urine collected during each collection interval (Vur), and renal clearance (CLr) all parts

  6. Pharmacodynamic response as measured by Bond and Lader visual analogue scale

    Time frame: Day 1 at multiple timepoints to 24h post dose.

    Changes in 3 factor scores (Alertness, Contentedness and Calmness) which will be derived from the individual VAS scores

  7. Pharmacodynamic response as measured by changes in qEEG and Event Related Potentials (ERP)

    Time frame: Screening, Day-1, Day 4, Day 9 multiple dosing regimen only

    qEEg and ERP (P50 sensory gating, Mismatch Negativity and P300)

Sponsors and collaborators

Lead sponsor

Nxera Pharma UK Limited

Industry

Registry information

Official study title

A Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of HTL0009936 in Healthy Subjects

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Nov 14, 2014
Registry last updated
Jun 20, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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