Clinical trial NCT02333487: Positron Emission Tomography (PET) Study Investigating Dopamine and Serotonin Receptor Occupancy After Multiple Oral Dosing of Lu AF35700
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2015-01-07
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Emax D1 Dopamine
timeFrame: Change from baseline to 344 hours post last dose
measure: EC50 D1 Dopamine
timeFrame: Change from baseline to 344 hours post last dose
measure: Emax D2 Dopamine
timeFrame: Change from baseline to 344 hours post last dose
measure: EC50 D2 Dopamine
timeFrame: Change from baseline to 344 hours post last dose
measure: Emax 5-HT6 Serotonin
timeFrame: Change from baseline to 344 hours post last dose
measure: EC50 5-HT6 Serotonin
timeFrame: Change from baseline to 344 hours post last dose
Secondary outcomes:
Other outcomes:
Locations:
city: Rockville
country: United States
facility: US802
state: Maryland
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck
role: STUDY_DIRECTOR
References: