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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02710188
• Other study ID #: 9936-104
• Secondary ID: 2015-004921-16
• Status: Completed
• Phase: Phase 1
• First received: March 2, 2016
• Last updated: October 17, 2016
• Start date: February 2016
• Est. completion date: August 2016

Study information

• Verified date: October 2016
• Source: Heptares Therapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• HTL0009936 modified release
HTL0009936 modified release
• HTL0009936 immediate release
HTL0009936 immediate release

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Ruddington	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
Heptares Therapeutics Limited	Quotient Clinical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tlag	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	No
Primary	Frel	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	No
Primary	Tmax	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	No
Primary	Cmax	The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax.	14 weeks	No
Primary	Concentration of HTL0009936 at 6 hours post dose (C6)	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	No
Primary	AUC (0-last)	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	No
Primary	AUC (0-inf)	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	No
Primary	AUC%extrap	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	No
Primary	Lambda-z	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	No
Primary	T1/2	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	No
Primary	Dose normalized AUC	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	No
Primary	Dose normalized Cmax	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	No
Primary	Concentration of HTL0009936 at 12 hours post dose (C12)	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	No
Primary	Concentration of HTL0009936 at 24 hours post dose (C24)	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	No