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

Lundbeck

Status and phase: Completed; Phase 1

Conditions: Schizophrenia

Treatments: Drug: Lu AF35700

Study type: Interventional

Funder types: Industry

Identifiers

NCT02333487

15859A

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. The patient experienced an acute exacerbation requiring hospitalization within the last 3 months.
2. The patient experienced an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 4 weeks.
3. The patient has a diagnosis or history of substance use disorder (except nicotine) according to DSM-5-TR® criteria ≤3 months prior to screening
4. 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.
5. 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.
6. The patient has had past episodes of extrapyramidal symptoms (EPS) under current medication within the last 3 month
7. The patient takes other medication than those listed as allowed concomitant medication in Appendix III
8. The patient is occupationally exposed to significant levels of ionizing radiation.

Other protocol-defined inclusion and exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 3 patient groups

Lu AF35700 (Group D1)

Experimental group

Description:

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

Treatment:

Drug: Lu AF35700

Lu AF35700 (Group D2)

Experimental group

Description:

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

Treatment:

Drug: Lu AF35700

Lu AF35700 (Group 5-HT6)

Experimental group

Description:

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

Treatment:

Drug: Lu AF35700