HealthyPhase 1NCT02406261

A Drug-Drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants

A Phase 1 study testing Lanabecestat, Simvastatin and Midazolam in people with Healthy, run by AstraZeneca at 2 sites in United States.

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

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Lanabecestat, Simvastatin and Midazolam
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 82 participants
Where: 2 sitesUnited States
Study dates: 30 Apr 2015to 31 Aug 2015
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Overtly healthy and either sterile or, male and prepared to use an approved method of contraception
Have a body mass index (BMI) at screening of 19.0 to 32.0 kilogram per square meter (kg/m^2)

Who cannot join

History of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
History of previous or ongoing psychiatric disease/condition

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Covance Inc
Dallas, Texas, 75247
Covance Inc
Daytona Beach, Florida, 32117

Other trials in United States

About this study

Official title: A Study to Characterize LY3314814 Pharmacokinetics as a Function of Dosing Duration and to Determine the Effect of LY3314814 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects

The purpose of this study is to study the effect of lanabecestat on how the body absorbs and processes 3 other medications, midazolam, simvastatin and donepezil and how these 3 medications affect lanabecestat when they are taken together. This study is in 2 cohorts, Cohort A is approximately 44 days long and Cohort B about 70 days only. The screening visit is required within 30 days prior to the start on the study

Read the detailed description

Astra Zeneca (AZ) registered this trial as sponsor. In July, 2015, sponsorship changed to Eli Lilly and Company (Lilly). In August, 2015, AZ transferred this trial to Lilly's ClinicalTrials.gov account and Lilly updated the record. This trial is not an applicable trial under the Food and Drug Administration Amendments Act of 2007 (FDAAA).

Conditions: Healthy
Being tested: Lanabecestat, Simvastatin, Midazolam, Donepezil

What participants receive

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

LanabecestatDrug
Also called LY3314814, AZD3293
50 mg lanabecestat will be administered orally as 1 × 50-mg tablet
SimvastatinDrug
20 mg simvastatin will be administered orally as 1 × 20-mg tablet
MidazolamDrug
500 mcg midazolam will be administered orally as 0.25 mL of 2-mg/mL syrup
MidazolamDrug
250 mcg midazolam will be administered intravenous (IV) as 0.25 mL of 1-mg/mL injection solution
DonepezilDrug
5 mg donepezil will be administered orally as 1 × 5-mg tablet
LanabecestatDrug
Also called LY3314814, AZD3293
50 mg lanabecestat will be administered orally as 1 × 50-mg tablet

Study groups in NCT02406261
Study group	Role	What they receive
Cohort A	Experimental	500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg lanabecestat, single oral dose on Day 4; 50 mg lanabecestat, single oral dose, Days 10 to 37 Receives: Drug: Lanabecestat; Drug: Simvastatin; Drug: Midazolam
Cohort B	Experimental	5 mg donepezil, single oral dose on Day 1, Period 1; 50 mg lanabecestat, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28, Period 2 Receives: Drug: Donepezil; Drug: Lanabecestat

What is being measured

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

Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
Measured: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)
PK Profile for Simvastatin: AUC(0-∞)
Measured: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
Measured: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)
PK Profile for Donepezil: AUC(0-∞)
Measured: Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B)

Secondary outcomes (2)

Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration
Measured: Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Measured: Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)

Timeline

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

30 Apr 201531 Aug 2015

First posted2 Apr 2015 (estimated)
Study start30 Apr 2015
Primary completion31 Aug 2015
Study completion31 Aug 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
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: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 82 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02406261
Sponsor's protocol ID: 16014
Other IDs: I8D-MC-AZER
Status last verified: Oct 2019
First submitted: 2 Mar 2015
Last updated: 4 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: 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?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Characterize LY3314814 Pharmacokinetics as a Function of Dosing Duration and to Determine the Effect of LY3314814 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects
ClinicalTrials.gov ID: NCT02406261
Acronym / sponsor ID: 16014
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 82 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: 30 Apr 2015 (actual)
Primary completion: 31 Aug 2015 (actual)
Study completion: 31 Aug 2015 (actual)
First posted: 2 Apr 2015 (estimated)
Results: Posted 22 Mar 2019

Clinical summary

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

Detailed description

Study design

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

Arm	Type	Receives
Cohort A	Experimental	Drug: Lanabecestat, Drug: Simvastatin, Drug: Midazolam500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg lanabecestat, single oral dose on Day 4; 50 mg lanabecestat, single oral dose, Days 10 to 37
Cohort B	Experimental	Drug: Donepezil, Drug: Lanabecestat5 mg donepezil, single oral dose on Day 1, Period 1; 50 mg lanabecestat, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28, Period 2

Who may qualify

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

Key inclusion criteria (2 listed)

Overtly healthy and either sterile or, male and prepared to use an approved method of contraception
Have a body mass index (BMI) at screening of 19.0 to 32.0 kilogram per square meter (kg/m^2)

Key exclusion criteria (3 listed)

History of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
History of previous or ongoing psychiatric disease/condition

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
LanabecestatAlso: LY3314814, AZD329350 mg lanabecestat will be administered orally as 1 × 50-mg tablet	Drug	Cohort A
Simvastatin20 mg simvastatin will be administered orally as 1 × 20-mg tablet	Drug	Cohort A
Midazolam500 mcg midazolam will be administered orally as 0.25 mL of 2-mg/mL syrup	Drug	Cohort A
Midazolam250 mcg midazolam will be administered intravenous (IV) as 0.25 mL of 1-mg/mL injection solution	Drug	Cohort A
Donepezil5 mg donepezil will be administered orally as 1 × 5-mg tablet	Drug	Cohort B
LanabecestatAlso: LY3314814, AZD329350 mg lanabecestat will be administered orally as 1 × 50-mg tablet	Drug	Cohort B

Primary outcome

Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
Time frame: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)
PK Profile for Simvastatin: AUC(0-∞)
Time frame: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
Time frame: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)
PK Profile for Donepezil: AUC(0-∞)
Time frame: Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B)

2 secondary outcomes

Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration
Time frame: Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)

Results and safety

Results posted to the registry on 22 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A	50	47
Cohort B	32	32

Primary outcome: Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814

Time frame: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A). Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram * hour per milliliter (ng*h/mL)

Measure	Cohort A n = 50
Value	3200 (21)

Population analysed: Participants who received at least one dose of study drug and had evaluable PK data.

Primary outcome: PK Profile for Simvastatin: AUC(0-∞)

Time frame: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A). Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Cohort A n = 49
AUC(0-∞) Simvastatin Day 2	15.1 (84)
AUC(0-∞) Simvastatin Day 36	21.2 (59)

Population analysed: Participants who received at least one dose of study drug and had evaluable PK data.

Primary outcome: PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose

Time frame: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A). Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Cohort A n = 49
AUC(0-∞) Oral Day 1	6.53 (38)
AUC(0-∞) Oral Day 17	6.24 (42)
AUC(0-∞) Oral Day 35	5.59 (40)
AUC(0-∞) IV Day 3	11.4 (22)
AUC(0-∞) IV Day 37	11.6 (21)

Population analysed: Participants who received at least one dose of study drug and had evaluable PK data.

Primary outcome: PK Profile for Donepezil: AUC(0-∞)

Time frame: Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B). Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Cohort B n = 31
Day 1	271 (28)
Day 28	285 (23)

Population analysed: Participants who received at least one dose of study drug and had evaluable PK data.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A	0 of 50 (0%)	6 of 50 (12%)	Not reported
Cohort B	0 of 32 (0%)	7 of 32 (21.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lanabecestat, Simvastatin and Midazolam in people with Healthy, run by AstraZeneca at 2 sites in United States.

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 2 inclusion and 3 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 4 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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?

Yes. Results are posted in the registry (first posted 22 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814 (time frame: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)). The study lists 4 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 NCT02406261.

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 4 Nov 2019.