Alzheimer's Disease
Conditions
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.
Interventions
DRUGHTL0009936 modified release
HTL0009936 modified release
DRUGHTL0009936 immediate release
HTL0009936 immediate release
Sponsors
Quotient Clinical
Nxera Pharma UK Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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) |
| 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 (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)) |
| 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)). |
| 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). |
| 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). |
| 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. |
| 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) |
Countries
United Kingdom
Outcome results
None listed