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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02291783
• Other study ID #: 9936-101
• Secondary ID: 2013-002307-34
• Status: Completed
• Phase: Phase 1
• First received: October 7, 2014
• Last updated: June 19, 2017
• Start date: November 2013
• Est. completion date: July 2014

Study information

• Verified date: June 2017
• Source: Heptares Therapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• HTL0009936
Single dose
• HTL0009936 placebo
Placebo single dose

Locations

Country	Name	City	State
United Kingdom	Parexel Early Phase Clinical Unit	Harrow	Middlesex

Sponsors (1)

Lead Sponsor	Collaborator
Heptares Therapeutics Limited

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events, as a measure of safety and tolerability	AE reports include a description of the AE, date and time of onset and resolution, intensity, and relationship to IMP.	From signing of informed consent up to 30 days after the final visit
Primary	Changes in Safety Lab parameters as a measure of safety and tolerability	Hematology, clinical chemistry, urinalysis	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.
Primary	Changes in vital signs as a measure of safety and tolerability	Pulse rate,body temperature,blood pressure, and orthostatic changes.	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.
Primary	Changes in 12-lead electrocardiograms as a measure of safety and tolerability	Change in ECG parameters	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	Pharmacokinetic measures in plasma as measured by Peak plasma concentration (Cmax)	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.	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.
Secondary	Pharmacokinetic measures in cerebro spinal fluid (CSF) in young males as measured by max observed CSF (Cmax CSF)	Maximum observed CSF concentration (Cmax CSF), area under the CSF concentration versus time	Part 1 - 1h, 2h,3h post dose
Secondary	Pharmacokinetic measures to assess the food effect as measured by ANOVA	Food effect analysis will be based on analysis of variance (ANOVA) for treatment differences.	Pre-dose, multiple time points to 24h, and at 12h, 24h and 5 to 7 days post dose.
Secondary	Pharmacodynamic response as measured by pupillometry	Changes in average pupil diameter as measured in 3 different conditions of lux.	Multiple time points Day1 to 6h post dose Part 1 only.
Secondary	Pharmacokinetic measures in urine in young males and elderly male and female subjects as measured by amount of urine excreted at collection intervals	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	Pre-dose,multiple 4h collection intervals to 24h post dose on select dosing days to Day 10 for multiple dosing.
Secondary	Pharmacodynamic response as measured by Bond and Lader visual analogue scale	Changes in 3 factor scores (Alertness, Contentedness and Calmness) which will be derived from the individual VAS scores	Day 1 at multiple timepoints to 24h post dose.
Secondary	Pharmacodynamic response as measured by changes in qEEG and Event Related Potentials (ERP)	qEEg and ERP (P50 sensory gating, Mismatch Negativity and P300)	Screening, Day-1, Day 4, Day 9 multiple dosing regimen only