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

NCT02291783 | Completed Phase 1

• 2 other identifiers: 9936-1012013-002307-34
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (4)

• 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

• 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.

• 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.

• 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 Outcomes (7)

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

  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.

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

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

• Pharmacokinetic measures to assess the food effect as measured by ANOVA

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

• Pharmacodynamic response as measured by pupillometry

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

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

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

Study Arms (2)

HTL0009936

EXPERIMENTAL

HTL0009936 single and multiple ascending oral doses.

Drug: HTL0009936

HTL0009936 Placebo

PLACEBO COMPARATOR

HTL0009936 matching placebo

Drug: HTL0009936 placebo

Interventions

HTL0009936 DRUG

Single dose

Also known as: 9936, HTL0009936

HTL0009936

HTL0009936 placebo DRUG

Placebo single dose

Also known as: Placebo

HTL0009936 Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nxera Pharma UK Limited: lead

Study Sites (1)

Parexel Early Phase Clinical Unit

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Annelize Koch, MBChB

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2014
• First Posted: November 14, 2014
• Study Start: November 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)