Positron Emission Tomography (PET) Study Investigating Dopamine and Serotonin Receptor Occupancy After Multiple Oral Dosing of Lu AF35700

A Phase 1 study testing Lu AF35700 in people with Schizophrenia, run by H. Lundbeck A/S at 1 site in United States.

Completed

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

Trial summary

The purpose of this PET study is to verify the binding of Lu AF35700 after multiple oral dosing at the dopamine and the serotonin receptors in male patients with schizophrenia. Read more about this study

Who is it for?: Ages 18 to 60 years, men only
Conditions the study is for: Schizophrenia
What is being tested?: Lu AF35700
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 22 participants
Where: 1 siteUnited States
Study dates: 30 Dec 2014to 11 Feb 2016
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 60 years
Men only
No healthy volunteers
Adult

Who may be able to join

The patient is a man aged between ≤18 and ≥60 years
BMI of ≥19 kg/m2 to ≤ 37 kg/m2
The patient has a primary diagnosis of schizophrenia according to DSM-5™ (code 295.90)
The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score ≤ 4 (moderately ill) at screening and safety baseline
The patient is currently under oral therapy with one or more of the antipsychotic medications listed in Appendix II.
The patient has a Positive and Negative Syndrome Scale (PANSS) total score ≤ 80
The patient has a score of ≤ 4 (moderate) on the following PANSS items at screening and at safety baseline: P7 (hostility), G8 (uncooperativeness)

Who cannot join

The patient experienced an acute exacerbation requiring hospitalization within the last 3 months.
The patient experienced an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 4 weeks.
The patient has a diagnosis or history of substance use disorder (except nicotine) according to DSM-5-TR® criteria ≤3 months prior to screening
The patient is at significant risk of harming himself or others according to the investigator's judgment or as indicated by an answer of "yes" to the question 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at the Screening Visit within the last six months on the lifetime version of C-SSRS.
Based on investigators judgment the patient has a medical or neurological disorder or treatment for such disorder that could interfere with the study treatment or impair treatment compliance.
The patient has had past episodes of extrapyramidal symptoms (EPS) under current medication within the last 3 month

Show all 9Show fewer

The patient takes other medication than those listed as allowed concomitant medication in Appendix III
The patient is occupationally exposed to significant levels of ionizing radiation.
Other protocol-defined inclusion and exclusion criteria may apply

Trial locations and contacts

1 site in 1 country.

United States1 site

US802
Rockville, Maryland, 20850

Other trials in United States

About this study

Official title: Interventional, Open-label, Positron Emission Tomography (PET) Study Investigating D1 Dopamine, D2 Dopamine, and 5-HT6 Serotonin Receptor Occupancy After Multiple Oral Dosing of Lu AF35700 in Male Patients With Schizophrenia

The purpose of this PET study is to verify the binding of Lu AF35700 after multiple oral dosing at the dopamine and the serotonin receptors in male patients with schizophrenia.

Read the detailed description

There were 3 to 4 cohorts of 2 patients per receptor group. Lu AF35700 was administered as multiple oral doses for up to 21 days before the PET scans were performed. The doses in all groups were selected with the aim of characterising the exposure response (occupancy) curve. The doses for all groups, with the exception of A1, B1, and C1, were subject to change within the dose range already investigated and found tolerable. The next dose for the groups was established at a dosing conference based on an evaluation of the occupancy obtained, and safety, tolerability, and pharmacokinetic data from all previous cohorts.

Conditions: Schizophrenia
Being tested: Lu AF35700
Medical subject headings: Schizophrenia

What participants receive

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

Lu AF35700Drug
5 mg tablets for oral administration

Study groups in NCT02333487
Study group	Role	What they receive
Lu AF35700 (Group D1)	Experimental	Up to 3 PET scans, besides baseline scan, using [11C]-NNC 112 tracer to detect D1 dopamine receptor occupancy before and after multiple oral dosing of Lu AF35700 Receives: Drug: Lu AF35700
Lu AF35700 (Group D2)	Experimental	Up to 3 PET scans, besides baseline scan, using [11C]-Raclopride to detect D2 dopamine receptor occupancy before and after multiple oral dosing of Lu AF35700 Receives: Drug: Lu AF35700
Lu AF35700 (Group 5-HT6)	Experimental	Up to 3 PET scans, besides baseline scan, using [11C]- Lu AE60157 tracer to detect 5-HT6 (5-hydroxytryptamine-6) receptor occupancy before and after multiple oral dosing of Lu AF35700 Receives: Drug: Lu AF35700

What is being measured

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

Emax D1 Dopamine
Maximal target occupancy (Emax) on the D1 dopamine receptor using PET with [11C]-NNC 112 tracer compound.
The relationship between systemic exposure of Lu AF35700 and D1 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Measured: Change from baseline to 344 hours post last dose
EC50 D1 Dopamine
Plasma concentration which gives 50% of Emax (EC50)
The relationship between systemic exposure of Lu AF35700 and D1 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Measured: Change from baseline to 344 hours post last dose
Emax D2 Dopamine
Maximal target occupancy (Emax) on the D2 dopamine receptor using PET with [11C]-Raclopride tracer compound.
The relationship between systemic exposure of Lu AF35700 and D2 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Emax was estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Measured: Change from baseline to 344 hours post last dose
EC50 D2 Dopamine
Plasma concentration which gives 50% of Emax (EC50)
The relationship between systemic exposure of Lu AF35700+Lu AF36152 and D2 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Measured: Change from baseline to 344 hours post last dose
Emax 5-HT6 Serotonin
Maximal target occupancy (Emax) on the 5-HT6 receptor using PET with [11C]-Lu AE60157 as tracer compound.
The relationship between systemic exposure of Lu AF35700+Lu AF36152 and 5-HT6 occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Emax was estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Measured: Change from baseline to 344 hours post last dose
EC50 5-HT6 Serotonin
Plasma concentration which gives 50% of Emax (EC50)
The relationship between systemic exposure of Lu AF35700+Lu AF36152 and 5_HT6 serotonin occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Measured: Change from baseline to 344 hours post last dose

Timeline

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

30 Dec 201411 Feb 2016

First posted7 Jan 2015 (estimated)
Study start30 Dec 2014
Primary completion11 Feb 2016
Study completion11 Feb 2016

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 SchizophreniaStudies of the same condition, open and under way.
More trials run by H. Lundbeck A/SThe 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: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02333487
Sponsor's protocol ID: 15859A
Status last verified: May 2020
First submitted: 6 Jan 2015
Last updated: 12 May 2020
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?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Interventional, Open-label, Positron Emission Tomography (PET) Study Investigating D1 Dopamine, D2 Dopamine, and 5-HT6 Serotonin Receptor Occupancy After Multiple Oral Dosing of Lu AF35700 in Male Patients With Schizophrenia
ClinicalTrials.gov ID: NCT02333487
Acronym / sponsor ID: 15859A
Conditions: Schizophrenia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: H. Lundbeck A/SIndustry (pharma, biotech, devices)
Study start: 30 Dec 2014 (actual)
Primary completion: 11 Feb 2016 (actual)
Study completion: 11 Feb 2016 (actual)
First posted: 7 Jan 2015 (estimated)
Results: Posted 12 May 2020

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 PET study is to verify the binding of Lu AF35700 after multiple oral dosing at the dopamine and the serotonin receptors in male patients with schizophrenia.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Lu AF35700 (Group D1)	Experimental	Drug: Lu AF35700Up to 3 PET scans, besides baseline scan, using [11C]-NNC 112 tracer to detect D1 dopamine receptor occupancy before and after multiple oral dosing of Lu AF35700
Lu AF35700 (Group D2)	Experimental	Drug: Lu AF35700Up to 3 PET scans, besides baseline scan, using [11C]-Raclopride to detect D2 dopamine receptor occupancy before and after multiple oral dosing of Lu AF35700
Lu AF35700 (Group 5-HT6)	Experimental	Drug: Lu AF35700Up to 3 PET scans, besides baseline scan, using [11C]- Lu AE60157 tracer to detect 5-HT6 (5-hydroxytryptamine-6) receptor occupancy before and after multiple oral dosing of Lu AF35700

Who may qualify

Ages: 18 to 60 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

The patient is a man aged between ≤18 and ≥60 years
BMI of ≥19 kg/m2 to ≤ 37 kg/m2
The patient has a primary diagnosis of schizophrenia according to DSM-5™ (code 295.90)
The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score ≤ 4 (moderately ill) at screening and safety baseline
The patient is currently under oral therapy with one or more of the antipsychotic medications listed in Appendix II.

Key exclusion criteria (9 listed)

The patient experienced an acute exacerbation requiring hospitalization within the last 3 months.
The patient experienced an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 4 weeks.
The patient has a diagnosis or history of substance use disorder (except nicotine) according to DSM-5-TR® criteria ≤3 months prior to screening
The patient is at significant risk of harming himself or others according to the investigator's judgment or as indicated by an answer of "yes" to the question 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at the Screening Visit within the last six months on the lifetime version of C-SSRS.
Based on investigators judgment the patient has a medical or neurological disorder or treatment for such disorder that could interfere with the study treatment or impair treatment compliance.

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
Lu AF357005 mg tablets for oral administration	Drug	Lu AF35700 (Group 5-HT6), Lu AF35700 (Group D1), Lu AF35700 (Group D2)

Primary outcome

Emax D1 Dopamine
Time frame: Change from baseline to 344 hours post last dose
Maximal target occupancy (Emax) on the D1 dopamine receptor using PET with [11C]-NNC 112 tracer compound. The relationship between systemic exposure of Lu AF35700 and D1 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
EC50 D1 Dopamine
Time frame: Change from baseline to 344 hours post last dose
Plasma concentration which gives 50% of Emax (EC50) The relationship between systemic exposure of Lu AF35700 and D1 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Emax D2 Dopamine
Time frame: Change from baseline to 344 hours post last dose
Maximal target occupancy (Emax) on the D2 dopamine receptor using PET with [11C]-Raclopride tracer compound. The relationship between systemic exposure of Lu AF35700 and D2 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Emax was estimated using one model for all post-baseline scans combined. No statistical testing was performed.
EC50 D2 Dopamine
Time frame: Change from baseline to 344 hours post last dose
Plasma concentration which gives 50% of Emax (EC50) The relationship between systemic exposure of Lu AF35700+Lu AF36152 and D2 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.
Emax 5-HT6 Serotonin
Time frame: Change from baseline to 344 hours post last dose
Maximal target occupancy (Emax) on the 5-HT6 receptor using PET with [11C]-Lu AE60157 as tracer compound. The relationship between systemic exposure of Lu AF35700+Lu AF36152 and 5-HT6 occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Emax was estimated using one model for all post-baseline scans combined. No statistical testing was performed.
EC50 5-HT6 Serotonin
Time frame: Change from baseline to 344 hours post last dose
Plasma concentration which gives 50% of Emax (EC50) The relationship between systemic exposure of Lu AF35700+Lu AF36152 and 5_HT6 serotonin occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.

Results and safety

Results posted to the registry on 12 May 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lu AF35700 (Group D1)	6	6
Lu AF35700 (Group D2)	8	6
Lu AF35700 (Group 5-HT6)	8	8

Primary outcome: Emax D1 Dopamine

Time frame: Change from baseline to 344 hours post last dose. Number (95% Confidence Interval). Unit: percentage

Measure	Lu AF35700 (Group D1) n = 6
Value	81.9 (73.5 to 90.4)

Primary outcome: EC50 D1 Dopamine

Time frame: Change from baseline to 344 hours post last dose. Number (95% Confidence Interval). Unit: ng/mL

Measure	Lu AF35700 (Group D1) n = 6
Value	1.4 (0.8 to 2.0)

Primary outcome: Emax D2 Dopamine

Time frame: Change from baseline to 344 hours post last dose. Number. Unit: percentage

Measure	Lu AF35700 (Group D2) n = 8
Value	102

Primary outcome: EC50 D2 Dopamine

Time frame: Change from baseline to 344 hours post last dose. Number (95% Confidence Interval). Unit: ng/mL

Measure	Lu AF35700 (Group D2) n = 8
Value	29.1 (15.9 to 42.4)

Adverse events

Time frame: Up to week 12.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lu AF35700 (Group D1)	1 of 6 (16.7%)	5 of 6 (83.3%)	0 of 6
Lu AF35700 (Group D2)	1 of 8 (12.5%)	6 of 8 (75%)	0 of 8
Lu AF35700 (Group 5-HT6)	1 of 8 (12.5%)	7 of 8 (87.5%)	0 of 8

Limitations and caveats (from the sponsor): An estimate of the confidence interval for the parameter Emax in the dopamine D2 receptor occupancy model was not calculable.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
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.

Email contact via H. Lundbeck study director

LundbeckClinicalTrials@lundbeck.com

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 Lu AF35700 in people with Schizophrenia, run by H. Lundbeck A/S at 1 site 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 7 inclusion and 9 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 12 May 2020. 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 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 12 May 2020). 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?

Emax D1 Dopamine (time frame: Change from baseline to 344 hours post last dose). The study lists 6 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 NCT02333487.

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 12 May 2020.