Relative Bioavailability Study in Healthy Subjects to Evaluate the Pharmacokinetics of HTL0009936 After One Dose of Prototype Formulation

October 17, 2016 updated by: Heptares Therapeutics Limited

A Phase 1 Relative Bioavailability Study in Healthy CYP2D6 Intermediate (IM) and Extensive Metaboliser (EM) Subjects, Designed to Evaluate the Pharmacokinetic (PK) Profile of HTL0009936 Following Single Dose Administration of Modified Release (MR) Prototype Formulations

The purpose of this study is to find a modified release oral tablet formulation for this drug, which will be safe and well tolerated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim of the study is to develop a modified release oral tablet formulation that maintains plasma concentrations within the target therapeutic range, and is safe and tolerable.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Nottingham
      • Ruddington, Nottingham, United Kingdom, NG11 6JS
        • Quotient Clinical

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy males & females
  • Aged 18 to 65 years
  • Body mass index of 18.0 to 35.0 kg/m2
  • CYP2D6 (intermediate or extensive metabolizer)

Exclusion Criteria:

  • Subjects with a resting heart rate (HR) >90 bpm, and/or systolic blood pressure (BP) >150 mmHg, and/or diastolic BP >90 mmHg
  • Subjects with QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms (males) or >470 ms (females)
  • Personal or family history of long QT syndrome or sudden death
  • Subjects who are CYP2D6 (poor or ultra-rapid metabolizer)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HTL0009936 modified release (MR) Formulation
Intervention: 5 different modified release formulations of HTL0009936, as a single dose
Drug: HTL0009936 modified release
HTL0009936 modified release
Active Comparator: HTL00009936 immediate release (IR) fasted
Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state
Drug: HTL0009936 immediate release
HTL0009936 immediate release

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tlag
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the elapsed time from dosing at which HTL0009936 was first quantifiable in a concentration vs time profile (Tlag).
14 weeks
Frel
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of relative bioavailability (Frel) of HTL0009936 MR prototype formulations compared to the IR reference formulation and, if applicable, MR prototype formulations in the fed state compared to fasted state.
14 weeks
Tmax
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the elapsed time from dosing at which the maximum observed HTL0009936 concentration (Cmax) was apparent (Tmax)
14 weeks
Cmax
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax.
14 weeks
Concentration of HTL0009936 at 6 hours post dose (C6)
Time Frame: 6 hours post dose
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 6 hours post-dose (C6)
6 hours post dose
AUC (0-last)
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the area under the concentration versus time curve from time zero to the last measurable concentration (AUC(0-last))
14 weeks
AUC (0-inf)
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the area under the concentration versus time curve from time zero to extrapolated to infinity (AUC(0-inf)).
14 weeks
AUC%extrap
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of percentage of AUC(0-inf) extrapolated beyond last measured time point (AUC%extrap).
14 weeks
Lambda-z
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the slope of the apparent elimination phase (Lambda-z).
14 weeks
T1/2
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the apparent elimination half-life (T1/2).
14 weeks
Dose normalized AUC
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. In addition, if different dose levels of the same prototype are administered, dose normalized AUC (AUC/D) will be calculated.
14 weeks
Dose normalized Cmax
Time Frame: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. In addition, if different dose levels of the same prototype are administered, dose normalized Cmax (Cmax/D) will be calculated.
14 weeks
Concentration of HTL0009936 at 12 hours post dose (C12)
Time Frame: 12 hours post dose
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 12 hours post-dose (C12)
12 hours post dose
Concentration of HTL0009936 at 24 hours post dose (C24)
Time Frame: 24 hours post dose
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 24 hours post-dose (C24)
24 hours post dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heptares Therapeutics Limited

Collaborators

Quotient Clinical

Investigators

  • Principal Investigator: Litza McKenzie, MBChB, Quotient Clinical

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

March 2, 2016

First Submitted That Met QC Criteria

March 15, 2016

First Posted (Estimate)

March 16, 2016

Study Record Updates

Last Update Posted (Estimate)

October 18, 2016

Last Update Submitted That Met QC Criteria

October 17, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9936-104
  • 2015-004921-16 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alzheimer's Disease

Clinical Trials on HTL0009936 modified release

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Russia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe