Relative Bioavailability Study in Healthy Subjects to Evaluate the Pharmacokinetics of HTL0009936 After One Dose of Prototype Formulation
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
HTL0009936 modified release
HTL0009936 immediate release
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease
Eligibility Criteria
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)
Sites / Locations
- Quotient Clinical
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
HTL0009936 modified release (MR) Formulation
HTL00009936 immediate release (IR) fasted
Arm Description
Intervention: 5 different modified release formulations of HTL0009936, as a single dose
Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state
Outcomes
Primary Outcome Measures
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).
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.
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)
Cmax
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)
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 (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))
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)).
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).
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).
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).
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.
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.
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)
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)
Secondary Outcome Measures
Full Information
NCT ID
NCT02710188
First Posted
March 2, 2016
Last Updated
October 17, 2016
Sponsor
Heptares Therapeutics Limited
Collaborators
Quotient Clinical
1. Study Identification
Unique Protocol Identification Number
NCT02710188
Brief Title
Relative Bioavailability Study in Healthy Subjects to Evaluate the Pharmacokinetics of HTL0009936 After One Dose of Prototype Formulation
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heptares Therapeutics Limited
Collaborators
Quotient Clinical
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HTL0009936 modified release (MR) Formulation
Arm Type
Experimental
Arm Description
Intervention: 5 different modified release formulations of HTL0009936, as a single dose
Arm Title
HTL00009936 immediate release (IR) fasted
Arm Type
Active Comparator
Arm Description
Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state
Intervention Type
Drug
Intervention Name(s)
HTL0009936 modified release
Intervention Description
HTL0009936 modified release
Intervention Type
Drug
Intervention Name(s)
HTL0009936 immediate release
Intervention Description
HTL0009936 immediate release
Primary Outcome Measure Information:
Title
Tlag
Description
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).
Time Frame
14 weeks
Title
Frel
Description
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.
Time Frame
14 weeks
Title
Tmax
Description
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)
Time Frame
14 weeks
Title
Cmax
Description
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax.
Time Frame
14 weeks
Title
Concentration of HTL0009936 at 6 hours post dose (C6)
Description
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)
Time Frame
6 hours post dose
Title
AUC (0-last)
Description
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))
Time Frame
14 weeks
Title
AUC (0-inf)
Description
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)).
Time Frame
14 weeks
Title
AUC%extrap
Description
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).
Time Frame
14 weeks
Title
Lambda-z
Description
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).
Time Frame
14 weeks
Title
T1/2
Description
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).
Time Frame
14 weeks
Title
Dose normalized AUC
Description
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.
Time Frame
14 weeks
Title
Dose normalized Cmax
Description
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.
Time Frame
14 weeks
Title
Concentration of HTL0009936 at 12 hours post dose (C12)
Description
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)
Time Frame
12 hours post dose
Title
Concentration of HTL0009936 at 24 hours post dose (C24)
Description
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)
Time Frame
24 hours post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Litza McKenzie, MBChB
Organizational Affiliation
Quotient Clinical
Official's Role
Principal Investigator
Facility Information:
Facility Name
Quotient Clinical
City
Ruddington
State/Province
Nottingham
ZIP/Postal Code
NG11 6JS
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Relative Bioavailability Study in Healthy Subjects to Evaluate the Pharmacokinetics of HTL0009936 After One Dose of Prototype Formulation
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