Alzheimer's DiseasePhase 1NCT02710188

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

A Phase 1 study testing HTL0009936 modified release and HTL0009936 immediate release in people with Alzheimer's Disease, run by Nxera Pharma UK Limited at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Alzheimer's Disease
What is being tested?: HTL0009936 modified release and HTL0009936 immediate release
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited Kingdom
Study dates: Feb 2016to Aug 2016
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Quotient Clinical
Ruddington, Nottingham, NG11 6JS

Other trials in United Kingdom

About this study

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

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

Read the 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.

Conditions: Alzheimer's Disease
Being tested: HTL0009936 modified release, HTL0009936 immediate release
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HTL0009936 modified releaseDrug
HTL0009936 modified release
HTL0009936 immediate releaseDrug
HTL0009936 immediate release

Study groups in NCT02710188
Study group	Role	What they receive
HTL0009936 modified release (MR) Formulation	Experimental	Intervention: 5 different modified release formulations of HTL0009936, as a single dose Receives: 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 Receives: Drug: HTL0009936 immediate release

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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)
Measured: 14 weeks
Cmax
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax.
Measured: 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)
Measured: 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))
Measured: 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)).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 24 hours post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2016Aug 2016

First posted16 Mar 2016 (estimated)
Study startFeb 2016
Primary completionJul 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02710188
Sponsor's protocol ID: 9936-104
Other IDs: 2015-004921-16, 2015
Status last verified: Oct 2016
First submitted: 2 Mar 2016
Last updated: 18 Oct 2016
Results posted: No
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02710188
Acronym / sponsor ID: 9936-104
Conditions: Alzheimer's Disease
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: Nxera Pharma UK LimitedIndustry (pharma, biotech, devices)
Collaborators: Quotient Clinical
Study start: Feb 2016
Primary completion: Jul 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 16 Mar 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
HTL0009936 modified release (MR) Formulation	Experimental	Drug: HTL0009936 modified releaseIntervention: 5 different modified release formulations of HTL0009936, as a single dose
HTL00009936 immediate release (IR) fasted	Active comparator	Drug: HTL0009936 immediate releaseIntervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (4 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
HTL0009936 modified releaseHTL0009936 modified release	Drug	HTL0009936 modified release (MR) Formulation
HTL0009936 immediate releaseHTL0009936 immediate release	Drug	HTL00009936 immediate release (IR) fasted

Primary outcome

Tlag
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2016.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Litza McKenzie, MBChB principal investigator

Quotient Clinical

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HTL0009936 modified release and HTL0009936 immediate release in people with Alzheimer's Disease, run by Nxera Pharma UK Limited at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tlag (time frame: 14 weeks). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02710188.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2016.