Phase 1 Study Investigating Effects of HTL0009936 on Cognition and BOLD fMRI Signals in Healthy Elderly Subjects

Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Phase 1, Exploratory Study Investigating the Effects of HTL0009936 on Cognition and BOLD fMRI Signals in Healthy Elderly Subjects

To determine if treatment with HTL0009936 will lead to changes in neural activity, measured using the fMRI BOLD signal and ASL, in brain areas that are associated with spatial and working memory, learning and executive functioning.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: HTL0009936; Drug: HTL0009936 matching placebo

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M13 9PT
    • Neuroscience and Psychiatry Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy on the basis of medical history, physical examination, vital signs, 12-lead ECG, haematology, blood chemistry, urinalysis and a pre-study psychological assessment.
• Mini Mental State Examination (MMSE) Score of ≥24.
• Intermediate or extensive metaboliser as determined by CYP2D6 genotype.
• Fluent English speaker.
• Right-handed.
• Not a regular smoker

Exclusion Criteria:

• Recreational drug use within 3 months prior to Screening Visit.
• Positive alcohol breath test.
• Positive urine drug screen.
• Consumption of large amounts of caffeinated drinks.
• Consumption of any food or any drinks containing cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges.
• Ultra-rapid or poor metabolizer as determined by CYP2D6 genotype.
• By self-report, taking two or more daytime naps per week which in the opinion of the investigator is likely to interfere with the ability of the subject to complete the study procedures.
• History of, or presents (in the opinion of the Investigator) with, significant neurological or psychiatric conditions.
• Personal or family history of congenital long QT syndrome or sudden death.
• Concomitant use of drugs that are metabolised by and/or are inhibitors of CYP2D6.
• Concomitant use of drugs that are substrates for the organic cation transporter 2.
• History of significant claustrophobia.
• Fulfils any of the MRI contraindications on the standard site radiography screening questionnaire (e.g. history of surgery involving metal implants).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HTL0009936 high dose; high dose infusion	Drug: HTL0009936
EXPERIMENTAL: HTL0009936 low dose; low dose infusion	Drug: HTL0009936
PLACEBO_COMPARATOR: HTL0009936 matching placebo; matching infusion	Drug: HTL0009936 matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood oxygen level dependent (BOLD) signal in functional Magnetic Resonance Imaging (fMRI) of the brain areas associated with cognitive tasks	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
BOLD signal in fMRI in other brain regions involved in the regulation of cognitive processes during cognitive tasks	Day 1
cerebral blood flow, assessed using Arterial Spin Labelling (ASL)	Day 1
adverse events	Day 1
blood pressure	Day 1
12-lead electrocardiogram	Day 1

Other Outcome Measures

Outcome Measure	Time Frame
event related potentials	Day 1

Collaborators and Investigators

• Sponsor: Heptares Therapeutics Limited
• Collaborators: P1vital Limited

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: September 1, 2015
• First Submitted That Met QC Criteria: September 8, 2015
• First Posted (ESTIMATE): September 10, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 3, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 9936-103