Back to results

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

Primary Purpose

Alzheimer's Disease

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

HTL0009936

HTL0009936 placebo

About this trial

This is an interventional treatment trial for Alzheimer's Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Parexel Early Phase Clinical Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

HTL0009936

HTL0009936 Placebo

Arm Description

HTL0009936 single and multiple ascending oral doses.

HTL0009936 matching placebo

Outcomes

Primary Outcome Measures

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.

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

Hematology, clinical chemistry, urinalysis

Changes in vital signs as a measure of safety and tolerability

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

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

Change in ECG parameters

Secondary Outcome Measures

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.

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

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.

Pharmacodynamic response as measured by pupillometry

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

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

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

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

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

Full Information

NCT ID

NCT02291783

First Posted

October 7, 2014

Last Updated

June 19, 2017

Sponsor

Heptares Therapeutics Limited

1. Study Identification

Unique Protocol Identification Number

NCT02291783

Brief Title

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

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

November 2013 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Heptares Therapeutics Limited

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

108 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HTL0009936

Arm Type

Experimental

Arm Description

HTL0009936 single and multiple ascending oral doses.

Arm Title

HTL0009936 Placebo

Arm Type

Placebo Comparator

Arm Description

HTL0009936 matching placebo

Intervention Type

Drug

Intervention Name(s)

HTL0009936

Other Intervention Name(s)

9936, HTL0009936

Intervention Description

Single dose

Intervention Type

Drug

Intervention Name(s)

HTL0009936 placebo

Other Intervention Name(s)

Placebo

Intervention Description

Placebo single dose

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

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

Title

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

Description

Hematology, clinical chemistry, urinalysis

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.

Title

Changes in vital signs as a measure of safety and tolerability

Description

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

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.

Title

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

Description

Change in ECG parameters

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.

Secondary Outcome Measure Information:

Title

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

Description

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.

Title

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

Description

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

Time Frame

Part 1 - 1h, 2h,3h post dose

Title

Pharmacokinetic measures to assess the food effect as measured by ANOVA

Description

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

Time Frame

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

Title

Pharmacodynamic response as measured by pupillometry

Description

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

Time Frame

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

Title

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

Description

Time Frame

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

Title

Pharmacodynamic response as measured by Bond and Lader visual analogue scale

Description

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

Time Frame

Day 1 at multiple timepoints to 24h post dose.

Title

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

Description

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

Time Frame

Screening, Day-1, Day 4, Day 9 multiple dosing regimen only

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Annelize Koch, MBChB

Organizational Affiliation

Parexel

Official's Role

Principal Investigator

Facility Information:

Facility Name

Parexel Early Phase Clinical Unit

City

Harrow

State/Province

Middlesex

ZIP/Postal Code

HA1 3UJ

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs