Measurement of HTL0016878 in Cerebrospinal Fluid

A Phase 1, Open-label, Randomised, Single-centre, Single Oral Dose Study to Determine the Concentration of HTL0016878 in Cerebrospinal Fluid and Plasma in Healthy Male Subjects Following Dosing With HTL0016878 Oral Solution

A Phase 1, open-label, randomised, single oral dose study to determine the concentration of HTL0016878 in CSF and plasma in healthy male subjects following dosing with HTL0016878 10 mg or 20 mg oral solution

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: HTL0016878

Detailed Description

Up to 24 healthy subjects will be enrolled into 4 groups, with 6 subjects per group. Each subject will be randomised to receive a single oral dose of 10 mg or 20 mg HTL0016878 solution and will have a single CSF sample taken via lumbar puncture at either 2 or 6 hours post-dose. Pharmacokinetic blood sampling and safety measures will continue until 24 hours post-dose.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M13 9NQ
    • MAC Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subject has a body mass index (BMI) of 18 to 32 kg/m2, inclusive. Healthy as determined by a responsible physician, based on medical evaluation including medical history, physical examination, concomitant medication, vital signs, 12-lead ECG, C-SSRS responses, and clinical laboratory evaluations.

Willingness to comply with requirements or the trial, including contraception requirements.

Able to give fully informed consent.

Exclusion Criteria:

Positive tests for hepatitis B & C, HIV. Clinically relevant history of abnormal physical or mental health. Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry or coagulation panel and urinalysis), 12-lead ECG and vital signs, or physical findings.

History of severe adverse reactions or allergies, or history of an anaphylactic reaction to prescription or non-prescription medication or food.

Drug or alcohol abuse. Smoking. Use of medication that inhibits CYP2D6. Participation in other clinical trials of unlicensed medicines in the previous 3 months. Loss of more than 400 mL blood in the previous 3 months. Vital signs, QTcF interval or laboratory values outside the acceptable range. Predicted poor and intermediate CYP2D6 metabolisers. Clinically relevant abnormal findings at the screening assessment. History of epilepsy or seizures. Clinically relevant abnormal medical history or concurrent medical condition disease associated with cognitive impairment and/or psychosis. History of suicidal thoughts or ideation, or any history of insomnia. Use of tobacco and/or nicotine containing products within 90 days of dosing. Habitual and heavy consumption of caffeinated beverages. Consumption of cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges (including marmalade and juices made from these fruits) within 3 days before admission. Objection by General Practitioner

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 10 mg dose, CSF sample 2 hours post-dose	Drug: HTL0016878; Oral solution
Experimental: Group 2; 10 mg dose, CSF sample 6 hours post-dose	Drug: HTL0016878; Oral solution
Experimental: Group 3; 20 mg dose, CSF sample 2 hours post-dose	Drug: HTL0016878; Oral solution
Experimental: Group 4; 20 mg dose, CSF sample 6 hours post-dose	Drug: HTL0016878; Oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of HTL0016878 in CSF	Pharmacokinetics	2 hours
Concentration of HTL0016878 in CSF	Pharmacokinetics	6 hours
Concentration of HTL0016878 in plasma Cmax	Pharmacokinetics	0-24 hours
Concentration of HTL0016878 in plasma AUC	Pharmacokinetics	0-24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Emergent Adverse events	Safety and Tolerability	Baseline up to 10 days post-dose

Collaborators and Investigators

• Sponsor: Heptares Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): December 7, 2018
• Study Completion (Actual): December 7, 2018

Study Registration Dates

• First Submitted: April 15, 2021
• First Submitted That Met QC Criteria: April 15, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 15, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Cerebrospinal Fluid
• Other Study ID Numbers: HTL0016878-103; 2018-002784-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No