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

NCT02710188 | Completed Phase 1 DMC

• 2 other identifiers: 9936-1042015-004921-16
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (14)

• 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

• 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

• 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

• Cmax

  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)

  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)

  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)

  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

  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

  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

  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

  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

  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)

  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)

  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

Study Arms (2)

HTL0009936 modified release (MR) Formulation

EXPERIMENTAL

Intervention: 5 different modified release formulations of HTL0009936, as a single dose

Drug: HTL0009936 modified release

HTL00009936 immediate release (IR) fasted

ACTIVE COMPARATOR

Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state

Drug: HTL0009936 immediate release

Interventions

HTL0009936 modified release DRUG

HTL0009936 modified release

HTL0009936 modified release (MR) Formulation

HTL0009936 immediate release DRUG

HTL0009936 immediate release

HTL00009936 immediate release (IR) fasted

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nxera Pharma UK Limited: lead
• Quotient Clinical: collaborator

Study Sites (1)

Quotient Clinical

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Litza McKenzie, MBChB

  Quotient Clinical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: March 16, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 18, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)