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

Heptares Therapeutics

Status and phase: Completed; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: HTL0009936 matching placebo; Drug: HTL0009936

Study type: Interventional

Funder types: Industry

Identifiers

NCT02546310

9936-103

Details and patient eligibility

About

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.

Enrollment: 54 estimated patients

Sex: All

Ages: 65 to 80 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

54 participants in 3 patient groups, including a placebo group

HTL0009936 high dose

Experimental group

Description:

high dose infusion

Treatment:

Drug: HTL0009936

HTL0009936 low dose

Experimental group

Description:

low dose infusion

Treatment:

Drug: HTL0009936

HTL0009936 matching placebo

Placebo Comparator group

Description:

matching infusion

Treatment:

Drug: HTL0009936 matching placebo