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

Phase 1

Completed

• Conditions: Alzheimer's Disease
• Interventions: Drug: HTL0009936 modified release; Drug: HTL0009936 immediate release

• Registration Number: NCT02710188
• Lead Sponsor: Heptares Therapeutics Limited

Brief 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.

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 Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-03-02
• Study First Submitted QC: 2016-03-15
• Study First Posted: 2016-03-16
• Primary Completion: 2016-07
• Study Completion: 2016-08
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-17
• Last Update Posted: 2016-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HTL0009936 modified release (MR) Formulation	HTL0009936 modified release	Intervention: 5 different modified release formulations of HTL0009936, as a single dose
HTL00009936 immediate release (IR) fasted	HTL0009936 immediate release	Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state

Primary Outcome Measures

Name	Time	Method
AUC (0-inf)	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)).
T1/2	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).
Dose normalized AUC	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.
Tlag	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).
Tmax	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)
Lambda-z	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).
Frel	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.
Cmax	14 weeks	The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax.
Concentration of HTL0009936 at 6 hours post dose (C6)	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)
AUC%extrap	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).
AUC (0-last)	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))
Dose normalized Cmax	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.
Concentration of HTL0009936 at 12 hours post dose (C12)	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)
Concentration of HTL0009936 at 24 hours post dose (C24)	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)

Trial Locations

Locations (1)

Quotient Clinical; 🇬🇧 Ruddington, Nottingham, United Kingdom